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1.
PLoS One ; 15(4): e0232099, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32330183

RESUMO

Food cues affect hunger and nutritional choices. Omnipresent stimulation with palatable food contributes to the epidemics of obesity. The objective of the study was to investigate the impact of food cues on appetite-related hormones and to assess the functionality of the secreted hormones on macronutrient uptake in healthy subjects. Additionally, we aimed at verifying differences in the response of total and active ghrelin to stimulation with food pictures and to a meal followed by the stimulation. We were also interested in the identification of factors contributing to response to food cues. We recruited healthy, non-obese participants for two independent cross-over studies. During the first study, the subjects were presented random non-food pictures on the first day and pictures of foods on the second day of the study. Throughout the second study, following the picture session, the participants were additionally asked to drink a milkshake. Concentrations of blood glucose, triglycerides and hunger-related hormones were measured. The results showed that concentrations of several hormones measured in the blood are interdependent. In the case of ghrelin and gastric inhibitory peptide (GIP) as well as ghrelin and glucagon-like peptide-1 (GLP-1), this co-occurrence relies on the visual cues. Regulation of total ghrelin concentration following food stimulation is highly individual and responders showed upregulated total ghrelin, while the concentration of active ghrelin decreases following a meal. Protein content and colour intensity of food pictures reversely correlated with participants' rating of the pictures. We conclude that observation of food pictures influences the concentration of several appetite-related hormones. The close link of visual clues to physiological responses is likely of clinical relevance. Additionally, the protein content of displayed foods and green colour intensity in pictures may serve as a predictor of subjective attractiveness of the presented meal.


Assuntos
Fome/fisiologia , Obesidade/psicologia , Estimulação Luminosa/métodos , Adolescente , Adulto , Apetite/fisiologia , Glicemia/metabolismo , Comportamento de Escolha/fisiologia , Sinais (Psicologia) , Comportamento Alimentar/fisiologia , Feminino , Polipeptídeo Inibidor Gástrico/sangue , Grelina/sangue , Peptídeo 1 Semelhante ao Glucagon/sangue , Humanos , Insulina/sangue , Masculino , Nutrientes , Peptídeo YY/sangue
2.
Br J Nutr ; 124(4): 407-417, 2020 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-32248846

RESUMO

This study investigated metabolic, endocrine, appetite and mood responses to a maximal eating occasion in fourteen men (mean: age 28 (sd 5) years, body mass 77·2 (sd 6·6) kg and BMI 24·2 (sd 2·2) kg/m2) who completed two trials in a randomised crossover design. On each occasion, participants ate a homogenous mixed-macronutrient meal (pizza). On one occasion, they ate until 'comfortably full' (ad libitum) and on the other, until they 'could not eat another bite' (maximal). Mean energy intake was double in the maximal (13 024 (95 % CI 10 964, 15 084) kJ; 3113 (95 % CI 2620, 3605) kcal) compared with the ad libitum trial (6627 (95 % CI 5708, 7547) kJ; 1584 (95 % CI 1364, 1804) kcal). Serum insulin incremental AUC (iAUC) increased approximately 1·5-fold in the maximal compared with ad libitum trial (mean: ad libitum 43·8 (95 % CI 28·3, 59·3) nmol/l × 240 min and maximal 67·7 (95 % CI 47·0, 88·5) nmol/l × 240 min, P < 0·01), but glucose iAUC did not differ between trials (ad libitum 94·3 (95 % CI 30·3, 158·2) mmol/l × 240 min and maximal 126·5 (95 % CI 76·9, 176·0) mmol/l × 240 min, P = 0·19). TAG iAUC was approximately 1·5-fold greater in the maximal v. ad libitum trial (ad libitum 98·6 (95 % CI 69·9, 127·2) mmol/l × 240 min and maximal 146·4 (95 % CI 88·6, 204·1) mmol/l × 240 min, P < 0·01). Total glucagon-like peptide-1, glucose-dependent insulinotropic peptide and peptide tyrosine-tyrosine iAUC were greater in the maximal compared with ad libitum trial (P < 0·05). Total ghrelin concentrations decreased to a similar extent, but AUC was slightly lower in the maximal v. ad libitum trial (P = 0·02). There were marked differences on appetite and mood between trials, most notably maximal eating caused a prolonged increase in lethargy. Healthy men have the capacity to eat twice the energy content required to achieve comfortable fullness at a single meal. Postprandial glycaemia is well regulated following initial overeating, with elevated postprandial insulinaemia probably contributing.


Assuntos
Afeto/fisiologia , Apetite/fisiologia , Hiperfagia/sangue , Refeições/fisiologia , Período Pós-Prandial/fisiologia , Adulto , Área Sob a Curva , Glicemia/análise , Índice de Massa Corporal , Estudos Cross-Over , Dipeptídeos/sangue , Ingestão de Energia/fisiologia , Polipeptídeo Inibidor Gástrico/sangue , Grelina/sangue , Peptídeo 1 Semelhante ao Glucagon/sangue , Humanos , Insulina/sangue , Masculino , Adulto Jovem
3.
Nutrients ; 12(2)2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32069846

RESUMO

Nutrient excess enhances glucose-dependent insulinotropic polypeptide (GIP) secretion, which may in turn contribute to the development of liver steatosis. We hypothesized that elevated GIP levels in obesity may affect markers of liver injury through microRNAs. The study involved 128 subjects (body mass index (BMI) 25-40). Fasting and postprandial GIP, glucose, insulin, and lipids, as well as fasting alanine aminotransferase (ALT), γ-glutamyltransferase (GGT), cytokeratin-18, fibroblast growth factor (FGF)-19, and FGF-21 were determined. TaqMan low density array was used for quantitative analysis of blood microRNAs. Fasting GIP was associated with ALT [ß = 0.16 (confidence interval (CI): 0.01-0.32)], triglycerides [ß = 0.21 (95% CI: 0.06-0.36], and FGF-21 [ß = 0.20 (95%CI: 0.03-0.37)]; and postprandial GIP with GGT [ß = 0.17 (95%CI: 0.03-0.32)]. The odds ratio for elevated fatty liver index (>73%) was 2.42 (95%CI: 1.02-5.72) for high GIP versus low GIP patients. The miRNAs profile related to a high GIP plasma level included upregulated miR-136-5p, miR-320a, miR-483-5p, miR-520d-5p, miR-520b, miR-30e-3p, and miR-571. Analysis of the interactions of these microRNAs with gene expression pathways suggests their potential contribution to the regulation of the activity of genes associated with insulin resistance, fatty acids metabolism, and adipocytokines signaling. Exaggerated fasting and postprandial secretion of GIP in obesity are associated with elevated liver damage markers as well as FGF-21 plasma levels. Differentially expressed microRNAs suggest additional, epigenetic factors contributing to the gut-liver cross-talk.


Assuntos
Fígado Gorduroso/sangue , Polipeptídeo Inibidor Gástrico/sangue , MicroRNAs/sangue , Obesidade/sangue , Adipocinas/sangue , Adulto , Idoso , Biomarcadores/sangue , Índice de Massa Corporal , Epigênese Genética , Jejum/sangue , Ácidos Graxos/sangue , Fígado Gorduroso/etiologia , Fígado Gorduroso/genética , Feminino , Fatores de Crescimento de Fibroblastos/sangue , Humanos , Insulina/sangue , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/genética , Razão de Chances , Período Pós-Prandial , Transdução de Sinais/genética
4.
Acta Diabetol ; 57(5): 583-587, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31848710

RESUMO

AIMS: Glucose-dependent insulinotropic polypeptide (GIP) is released primarily from the proximal small intestine and glucagon-like peptide-1 (GLP-1) from the more distal small intestine and colon. Their relative importance to the incretin effect in health has been contentious in the past, although it now appears that GIP has the dominant role. It is uncertain whether there is a relationship between GIP and GLP-1 secretion. We aimed to evaluate the relationship between plasma GIP and GLP-1 responses to a 75-g oral glucose load in individuals with normal (NGT) and impaired glucose tolerance (IGT). METHODS: One hundred healthy subjects had measurements of blood glucose, serum insulin, plasma GIP and GLP-1 concentrations for 240 min after a 300 mL drink containing 75 g glucose. RESULTS: Fifty had NGT and 41 IGT; 9 had type 2 diabetes and were excluded from analysis. In both groups, there were increases in plasma GIP and GLP-1 following the glucose drink, with no difference in the magnitude of the responses between t = 0-240 min. There was a weak relationship between the iAUC0-240 min for GIP and GLP-1 in the combined (r = 0.23, P = 0.015) and in the IGT (r = 0.34, P = 0.01), but not in the NGT (r = 0.15, P = 0.14) group. CONCLUSIONS: There is a weak relationship between oral glucose-induced GIP and GLP-1 secretions in non-diabetic subjects.


Assuntos
Polipeptídeo Inibidor Gástrico/sangue , Peptídeo 1 Semelhante ao Glucagon/sangue , Intolerância à Glucose/sangue , Idoso , Glicemia/análise , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/sangue , Feminino , Teste de Tolerância a Glucose , Humanos , Insulina/sangue , Masculino
5.
Am J Clin Nutr ; 111(1): 28-41, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31742316

RESUMO

BACKGROUND: Altered meal-related gut hormone secretion seems important for weight loss and diabetes remission after Roux-en-Y gastric bypass (RYGB). Elucidating the responsible meal components and receptors could aid discovery of new treatments of obesity and diabetes. Enteroendocrine cells respond to digestion products of dietary triacylglycerol, especially long-chain fatty acids (LCFAs) and 2-oleoyl-glycerol (2-OG), but not medium-chain fatty acids (MCFAs). OBJECTIVE: We examined the impact of olive oil (20 mL) and its derivates, LCFAs and 2-OG, on enteroendocrine secretions [glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), cholecystokinin (CCK), peptide YY (PYY), and neurotensin (NT)] and on glucose, lipid, and bile acid metabolism in RYGB-operated and unoperated individuals. METHODS: In an exploratory randomized crossover design, 10 RYGB-operated patients and 10 matched controls ingested 3 equimolar triacylglycerol formulations on separate days: olive oil (digested to 2-OG + LCFAs), C8-dietary oil (2-OG + MCFAs), and tricaprylin (MCFAs; negative control). Hormone responses were calculated as area under the curve (AUC). RESULTS: Independent of group status, olive oil had greater effects than C8-dietary oil on AUCs of plasma GLP-1 (+32%; 95% CI: 23%, 43%; P < 0.01), CCK (+53%, P < 0.01), and NT (+71%, P < 0.01), whereas the effect on GIP differed between groups (+90% in controls, P < 0.01; +24% in RYGB, P = 0.10). Independent of group status, C8-dietary oil had greater effects than tricaprylin on AUCs of plasma CCK (+40%, P < 0.01) and NT (+32%, P < 0.01), but not GLP-1 (+5%; 95% CI: -2.9%, 13%; P = 0.22), whereas the effect on GIP again differed between groups (+78% in controls, P < 0.01; +39% in RYGB, P = 0.01). Distal (GLP-1/PYY/NT), but not proximal (CCK/GIP), enteroendocrine responses were generally greater in RYGB patients than in controls. CONCLUSIONS: The combination of LCFAs plus 2-OG was substantially more effective than 2-OG plus MCFAs in stimulating enteroendocrine secretion in RYGB-operated and matched control individuals. Distal lipid-induced gut hormone release was greater after RYGB.This trial was registered at clinicaltrials.gov as NCT03223389.


Assuntos
Gorduras na Dieta/metabolismo , Mucosa Intestinal/metabolismo , Obesidade/cirurgia , Adulto , Colecistocinina/sangue , Feminino , Derivação Gástrica , Polipeptídeo Inibidor Gástrico/sangue , Hormônios Gastrointestinais/sangue , Peptídeo 1 Semelhante ao Glucagon/sangue , Glicerídeos/metabolismo , Humanos , Masculino , Obesidade/sangue , Obesidade/metabolismo , Peptídeo YY/sangue , Triglicerídeos/metabolismo
6.
BMC Vet Res ; 15(1): 345, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31619223

RESUMO

BACKGROUND: The oral glucose test (OGT) is a useful tool for diagnosing insulin dysregulation (ID) and is somewhat repeatable in ponies under consistent management. This study aimed to determine whether the insulin and incretin responses to an OGT in ponies differed after short-term access to fertilised pasture, compared to unfertilised pasture, by using a randomised, repeated measures study design. Sixteen mixed-breed ponies were classified as severely insulin-dysregulated (SD; post-prandial insulin ≥80 µIU/mL) or not severely insulin-dysregulated (NSD; post-prandial insulin < 80 µIU/mL) using an OGT prior to the study. The ponies accessed pasture that was fertilised, or unfertilised, for 5 days (4 h/day, with supplemental hay provided at 0.7% bodyweight), with a 10 day period between phases. An OGT was performed after each phase. Glucose, insulin, active glucagon-like peptide-1 (aGLP-1), and glucose-dependent insulinotropic polypeptide (GIP) were measured in post-prandial blood samples. RESULTS: The volume of fertilised pasture was five-fold greater than unfertilised pasture, with % non-structural carbohydrates (NSC) similar between all forages. Consuming fertilised pasture increased (P = 0.018) the serum insulin response to an OGT, compared to grazing unfertilised pasture. A limitation of the study was that pasture intake was unable to be quantified. Insulin responses were greater in SD, compared to NSD, ponies (P < 0.001) and remained well above the test cut-off at all times. A subset of ponies, initially screened as NSD, became (more) insulin-dysregulated after pasture access. Further, aGLP-1 was a significant predictor of insulin concentration in this cohort. CONCLUSIONS: Whereas some insulin-dysregulated ponies were comparatively resistant to dietary intervention, others showed markedly different OGT responses following subtle changes in their forage-based diet. This implies that mild/early ID might be unmasked by dietary change, and that dietary management is important in these ponies. However, dietary management alone may not be adequate for all cases of ID.


Assuntos
Dieta/veterinária , Teste de Tolerância a Glucose/veterinária , Doenças dos Cavalos/metabolismo , Hiperinsulinismo/veterinária , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Estudos Cross-Over , Polipeptídeo Inibidor Gástrico/sangue , Peptídeo 1 Semelhante ao Glucagon/sangue , Cavalos , Hiperinsulinismo/metabolismo , Incretinas/sangue , Insulina/sangue , Síndrome Metabólica/veterinária , Fragmentos de Peptídeos/sangue , Queensland , Distribuição Aleatória
7.
Int J Mol Sci ; 20(18)2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31509948

RESUMO

As glucose-dependent insulinotropic polypeptide (GIP) possesses pro-adipogenic action, the suppression of the GIP hypersecretion seen in obesity might represent a novel therapeutic approach to the treatment of obesity. However, the mechanism of GIP hypersecretion remains largely unknown. In the present study, we investigated GIP secretion in two mouse models of obesity: High-fat diet-induced obese (DIO) mice and leptin-deficient Lepob/ob mice. In DIO mice, plasma GIP was increased along with an increase in GIP mRNA expression in the lower small intestine. Despite the robust alteration in the gut microbiome in DIO mice, co-administration of maltose and the α-glucosidase inhibitor (α-GI) miglitol induced the microbiome-mediated suppression of GIP secretion. The plasma GIP levels of Lepob/ob mice were also elevated and were suppressed by fat transplantation. The GIP mRNA expression in fat tissue was not increased in Lepob/ob mice, while the expression of an interleukin-1 receptor antagonist (IL-1Ra) was increased. Fat transplantation suppressed the expression of IL-1Ra. The plasma IL-1Ra levels were positively correlated with the plasma GIP levels. Accordingly, although circulating GIP levels are increased in both DIO and Lepob/ob mice, the underlying mechanisms differ, and the anti-obesity actions of α-GIs and leptin sensitizers may be mediated partly by the suppression of GIP secretion.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Polipeptídeo Inibidor Gástrico/metabolismo , Leptina/deficiência , Obesidade/metabolismo , Animais , Polipeptídeo Inibidor Gástrico/sangue , Polipeptídeo Inibidor Gástrico/genética , Expressão Gênica , Proteína Antagonista do Receptor de Interleucina 1/sangue , Proteína Antagonista do Receptor de Interleucina 1/genética , Proteína Antagonista do Receptor de Interleucina 1/metabolismo , Leptina/genética , Masculino , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/etiologia , Obesidade/genética , Receptores Acoplados a Proteínas-G/genética , Receptores Acoplados a Proteínas-G/metabolismo , Receptores dos Hormônios Gastrointestinais/genética , Receptores dos Hormônios Gastrointestinais/metabolismo
8.
J Nutr Biochem ; 73: 108221, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31522082

RESUMO

Green tea polyphenols, particularly catechins, decrease fasting and postprandial glucose. However, no studies have compared the timing of green tea ingestion on glucose metabolism and changes in catechin concentrations. Here, we examined the effects of timing of acute catechin-rich green tea ingestion on postprandial glucose metabolism in young men. Seventeen healthy young men completed four trials involving blood collection in a fasting state and at 30, 60, 120, and 180 min after meal consumption in a random order: 1) morning placebo trial (09:00 h; MP trial), 2) evening placebo trial (17:00 h; EP trial), 3) morning catechin-rich green tea trial (09:00 h; MGT trial), and 4) evening catechin-rich green tea trial (17:00 h; EGT trial). The concentrations of glucose at 120 min (P=.031) and 180 min (P=.013) after meal intake were significantly higher in the MGT trials than in the MP trials. Additionally, the concentration of glucose was significantly lower in EGT trials than in the EP trials at 60 min (P=.014). Moreover, the concentrations of glucose-dependent insulinotropic polypeptide were significantly lower in the green tea trials than in the placebo trials at 30 min (morning: P=.010, evening: P=.006) and 60 min (morning: P=.001, evening: P=.006) after meal intake in both the morning and evening trials. Our study demonstrated that acute ingestion of catechin-rich green tea in the evening reduced postprandial plasma glucose concentrations.


Assuntos
Glicemia/análise , Catequina/administração & dosagem , Ritmo Circadiano , Período Pós-Prandial , Chá , Adulto , Catequina/análogos & derivados , Estudos Cross-Over , Método Duplo-Cego , Jejum , Ácidos Graxos não Esterificados/sangue , Polipeptídeo Inibidor Gástrico/sangue , Peptídeo 1 Semelhante ao Glucagon/sangue , Humanos , Insulina/sangue , Masculino , Refeições , Placebos , Fatores de Tempo , Triglicerídeos/sangue , Adulto Jovem
9.
Nutr J ; 18(1): 52, 2019 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477157

RESUMO

BACKGROUND: Given the major role of glucose-dependent insulinotropic polypeptide (GIP) in the regulation of adiposity, this study examined the effects induced by a diet based on the Japanese tradition (SMART WASHOKU) on the visceral fat area (VFA) and GIP secretions. METHODS: Overweight/obese men (n = 21; mean age, 41.0 ± 9.0 years; mean BMI, 25.2 ± 2.0 kg/m2) without diabetes were placed on either a SMART WASHOKU or control meal for 2 weeks, in a randomized, cross-over setup with a four-week washout period. RESULTS: For the meal tolerance test, blood samples were collected at 0, 30, 60, 120, 180, and 240 min post-meal, followed by measuring blood glucose, insulin, GIP, and glucagon-like peptide-1 (GLP-1) levels. Relative to a control meal, SMART WASHOKU meal yielded significantly lower plasma postprandial GIP concentrations (AUC: 700.0 ± 208.0 vs. 1117.0 ± 351.4 pmol/L・4 h, P < 0.05); however, between meals, there was no significant difference in the levels of GLP-1, peptide YY, and ghrelin. Compared to the control meal, SMART WASHOKU intervention significantly reduced VFA and the levels of LDL-cholesterol, triglyceride, and HbA1c after the chronic meal intervention. CONCLUSIONS: In conclusion, a SMART WASHOKU meal may decrease VFA and improve metabolic parameters in overweight/obese men, possibly via suppressing GIP secretion.


Assuntos
Dieta/métodos , Polipeptídeo Inibidor Gástrico/sangue , Gordura Intra-Abdominal , Sobrepeso/sangue , Sobrepeso/dietoterapia , Adulto , Colesterol/sangue , Estudos Cross-Over , Grelina/sangue , Humanos , Masculino , Peptídeo YY/sangue , Triglicerídeos/sangue
10.
Nutrients ; 11(9)2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31484331

RESUMO

Resistant starch (RS) has been shown to improve postprandial glycemia and insulin sensitivity in adults with metabolic syndrome. RS is found naturally in potatoes, where the amount varies based on cooking method and serving temperature. Thirty females with a mean BMI of 32.8 ± 3.7 kg/m2, fasting glucose of 110.5 mg/dL, and insulin of 10.3 µIU/L, completed this randomized, crossover study. A quantity of 250 g of boiled (low RS) and baked then chilled (high RS) russet potatoes were consumed on two separate occasions. Glycemic (glucose and insulin) and incretin response, subjective satiety, and dietary intake were measured. Results showed that the chilled potato elicited significant reductions at 15 and 30 min in glucose (4.8% and 9.2%), insulin (25.8% and 22.6%), and glucose-dependent insulinotropic peptide (GIP) (41.1% and 37.6%), respectively. The area under the curve for insulin and GIP were significantly lower after the chilled potato, but no differences were seen in glucose, glucagon-like peptide-1, and peptide YY, or overall subjective satiety. A higher carbohydrate and glycemic index but lower fat diet was consumed 48-hours following the chilled potato than the boiled potato. This study demonstrates that consuming chilled potatoes higher in RS can positively impact the glycemic response in females with elevated fasting glucose and insulin.


Assuntos
Glicemia , Temperatura Baixa , Culinária , Polipeptídeo Inibidor Gástrico/sangue , Insulina/sangue , Solanum tuberosum , Adulto , Biomarcadores , Estudos Cross-Over , Feminino , Polipeptídeo Inibidor Gástrico/metabolismo , Humanos , Sobrepeso , Período Pós-Prandial , Adulto Jovem
11.
Peptides ; 122: 170155, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31539554

RESUMO

This paper describes the early history of Gastric Inhibitory Polypeptide, better referred to simply as GIP, from its isolation by purification from a crude preparation of CCK-PZ (cholecystokinin/pancreozymin) to its recognition as a key player in the pathogenesis of obesity and other metabolic disorders far removed from the enterogastrone properties by which it was originally identified. Augmentation of glucose mediated insulin release, the incretin effect, was discovered soon after GIP was first isolated and only much later was its important role in the pathogenesis of obesity, through mechanism other than insulin secretion, appreciated. Immunoassay - the only method by which the concentration of GIP was measured in plasma until quite recently - was found to be flawed and to depend upon which specific epitope of the hormone an assay detected. This was especially true if it was an amino-acid sequence specific to porcine rather than human GIP. A further confounder was the discovery that much of the GIP measured by immunoassay was its biological antagonist produced by cleavage of its two N-terminal amino-acids in the circulation by the same dipeptidyl-peptidase as de-activates GLP-1. Potential use of synthetic agonistic and antagonistic GIP analogues in therapeutics was barely alluded to before year 2000.


Assuntos
Polipeptídeo Inibidor Gástrico/genética , Glucose/metabolismo , Insulina/genética , Obesidade/genética , Colecistocinina/metabolismo , Epitopos/genética , Polipeptídeo Inibidor Gástrico/análogos & derivados , Polipeptídeo Inibidor Gástrico/sangue , Polipeptídeo Inibidor Gástrico/uso terapêutico , Hormônios Gastrointestinais/metabolismo , Peptídeo 1 Semelhante ao Glucagon/genética , Receptores de Peptídeos Semelhantes ao Glucagon/genética , Glucose/genética , Humanos , Incretinas/genética , Insulina/metabolismo , Obesidade/sangue , Obesidade/patologia , Peptídeos/metabolismo
12.
J Clin Endocrinol Metab ; 104(12): 6201-6206, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31393567

RESUMO

CONTEXT: It is not known whether glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) levels correlate within individuals, nor whether levels change with age. Previous studies have all been cross-sectional in design. OBJECTIVE: To evaluate longitudinal changes in fasting and glucose-stimulated incretin hormone concentrations in healthy older subjects. PATIENTS AND DESIGN: Forty-one healthy older subjects had measurements of plasma GLP-1 and GIP while fasting and after a 75-g oral glucose load on two occasions separated by 5.9 ± 0.1 years [mean age at the initial study: 71.2 ± 3.8 (SD) years]. Breath samples were collected to calculate the gastric 50% emptying time (T50). RESULTS: For GLP-1, both fasting concentrations (P < 0.001) and area under the curve 0 to 120 minutes (P = 0.001) were decreased at followup. Fasting GIP was also lower (P = 0.03) at follow up, but there was no change in the area under the curve 0 to 120 minutes (P = 0.26). The gastric emptying T50 was slower at followup (P = 0.008). Neither the change in T50 nor the body mass index at the initial study was a determinant of the change in incretin responses. Between the two study days, fasting GIP (r = 0.72, P < 0.001) correlated well, but not fasting GLP-1 (r = 0.23, P = 0.18). However, both glucose-stimulated GLP-1 (r = 0.50, P = 0.002) and GIP (r = 0.60, P < 0.001) showed correlations between the initial and follow-up studies. CONCLUSIONS: Fasting GIP and glucose-stimulated GLP-1 and GIP concentrations correlate within individuals over a follow-up period of ∼5.9 years. Aging is associated with reductions in fasting GLP-1 and GIP, and glucose-stimulated GLP-1, which may predispose to the development of glucose intolerance and type 2 diabetes.


Assuntos
Biomarcadores/sangue , Glicemia/análise , Jejum , Polipeptídeo Inibidor Gástrico/sangue , Peptídeo 1 Semelhante ao Glucagon/sangue , Intolerância à Glucose/sangue , Idoso , Estudos Transversais , Feminino , Seguimentos , Intolerância à Glucose/fisiopatologia , Teste de Tolerância a Glucose , Voluntários Saudáveis , Humanos , Estudos Longitudinais , Masculino , Prognóstico
13.
J Clin Endocrinol Metab ; 104(11): 5703-5714, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31390002

RESUMO

OBJECTIVE: Augmenting nicotinamide adenine dinucleotide (NAD+) metabolism through dietary provision of NAD+ precursor vitamins translates to improved glucose handling in rodent models of obesity and diabetes. Preclinical evidence suggests that the NAD+/SIRT1 axis may be implicated in modulating important gut-related aspects of glucose regulation. We sought to test whether NAD+ precursor supplementation with nicotinamide riboside (NR) affects ß-cell function, α-cell function, and incretin hormone secretion as well as circulating bile acid levels in humans. DESIGN: A 12-week randomized, double-blind, placebo-controlled, parallel-group trial in 40 males with obesity and insulin resistance allocated to NR at 1000 mg twice daily (n = 20) or placebo (n = 20). Two-hour 75-g oral glucose tolerance tests were performed before and after the intervention, and plasma concentrations of glucose, insulin, C-peptide, glucagon, glucagon-like peptide 1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) were determined. ß-Cell function indices were calculated based on glucose, insulin, and C-peptide measurements. Fasting plasma concentrations of bile acids were determined. RESULTS: NR supplementation during 12 weeks did not affect fasting or postglucose challenge concentrations of glucose, insulin, C-peptide, glucagon, GLP-1, or GIP, and ß-cell function did not respond to the intervention. Additionally, no changes in circulating adipsin or bile acids were observed following NR supplementation. CONCLUSION: The current study does not provide evidence to support that dietary supplementation with the NAD+ precursor NR serves to impact glucose tolerance, ß-cell secretory capacity, α-cell function, and incretin hormone secretion in nondiabetic males with obesity. Moreover, bile acid levels in plasma did not change in response to NR supplementation.


Assuntos
Glicemia , Polipeptídeo Inibidor Gástrico/sangue , Peptídeo 1 Semelhante ao Glucagon/sangue , Glucagon/sangue , Ilhotas Pancreáticas/efeitos dos fármacos , Niacinamida/análogos & derivados , Obesidade/sangue , Peptídeo C/sangue , Método Duplo-Cego , Teste de Tolerância a Glucose , Humanos , Insulina/sangue , Ilhotas Pancreáticas/fisiopatologia , Masculino , Pessoa de Meia-Idade , Niacinamida/farmacologia , Obesidade/fisiopatologia
14.
Diabet Med ; 36(11): 1367-1374, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31466128

RESUMO

AIM: To investigate the incretin axis in people with cystic fibrosis. METHODS: Adults with cystic fibrosis-related diabetes, cystic fibrosis without diabetes, and controls (adults without cystic fibrosis and without diabetes) underwent an oral glucose tolerance test and then a closely matched isoglycaemic i.v. glucose infusion. On each occasion, glucose, insulin, C-peptide, total and active glucagon-like peptide-1 and gastric inhibitory polypeptide responses were recorded and incremental areas under curves were calculated for 60 and 240 min. RESULTS: Five adults with cystic fibrosis-related diabetes, six with cystic fibrosis without diabetes and six controls, matched for age and BMI, completed the study. Glucose during oral glucose tolerance test closely matched those during isoglycaemic i.v. glucose infusion. The calculated incretin effect was similar in the control group and the cystic fibrosis without diabetes group (28% and 29%, respectively), but was lost in the cystic fibrosis-related diabetes group (cystic fibrosis-related diabetes vs control group: -6% vs 28%; p=0.03). No hyposecretion of glucagon-like peptide-1 or gastric inhibitory polypeptide was observed; conversely, 60-min incremental area under the curve for total glucagon-like peptide-1 was significantly higher in the cystic fibrosis-related diabetes group than in the control group [1070.4 (254.7) vs 694.97 (308.1); p=0.03] CONCLUSIONS: The incretin effect was lost in cystic fibrosis-related diabetes despite adequate secretion of the incretin hormones. These data support the concept that reduced incretin hormone insulinotropic activity contributes significantly to postprandial hyperglycaemia in cystic fibrosis-related diabetes.


Assuntos
Fibrose Cística/fisiopatologia , Diabetes Mellitus/fisiopatologia , Glucose/administração & dosagem , Hiperglicemia/fisiopatologia , Incretinas/sangue , Adulto , Peptídeo C/sangue , Fibrose Cística/complicações , Diabetes Mellitus/sangue , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/etiologia , Feminino , Polipeptídeo Inibidor Gástrico/sangue , Peptídeo 1 Semelhante ao Glucagon/sangue , Glucose/metabolismo , Teste de Tolerância a Glucose , Humanos , Hiperglicemia/sangue , Infusões Intravenosas , Insulina/sangue , Masculino
15.
Nutrients ; 11(7)2019 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-31261732

RESUMO

Oral diabetes-specific nutritional supplements (ONS-D) induce favourable postprandial responses in subjects with type 2 diabetes (DM2), but they have not been correlated yet with incretin release and subjective appetite (SA). This randomised, double-blind, cross-over study compared postprandial effects of ONS-D with isomaltulose and sucromalt versus standard formula (ET) on glycaemic index (GI), insulin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1) and SA in 16 individuals with DM2. After overnight fasting, subjects consumed a portion of supplements containing 25 g of carbohydrates or reference food. Blood samples were collected at baseline and at 30, 60, 90, 120, 150 and 180 min; and SA sensations were assessed by a visual analogue scale on separate days. Glycaemic index values were low for ONS-D and intermediate for ET (p < 0.001). The insulin area under the curve (AUC0-180 min) (p < 0.02) and GIP AUC (p < 0.02) were lower after ONS-D and higher GLP-1 AUC when compared with ET (p < 0.05). Subjective appetite AUC was greater after ET than ONS-D (p < 0.05). Interactions between hormones, hunger, fullness and GI were found, but not within the ratings of SA; isomaltulose and sucromalt may have influenced these factors.


Assuntos
Regulação do Apetite , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/dietoterapia , Suplementos Nutricionais , Dissacarídeos/administração & dosagem , Frutose/administração & dosagem , Índice Glicêmico , Isomaltose/administração & dosagem , Hormônios Peptídicos/sangue , Administração Oral , Biomarcadores/sangue , Estudos Cross-Over , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/psicologia , Dissacarídeos/efeitos adversos , Método Duplo-Cego , Feminino , Frutose/efeitos adversos , Polipeptídeo Inibidor Gástrico/sangue , Peptídeo 1 Semelhante ao Glucagon/sangue , Humanos , Insulina/sangue , Isomaltose/efeitos adversos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento
16.
J Clin Endocrinol Metab ; 104(12): 6403-6416, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31276156

RESUMO

CONTEXT: After Roux-en-Y gastric bypass (RYGB) surgery, postprandial plasma glucagon concentrations have been reported to increase. This occurs despite concomitant improved glucose tolerance and increased circulating plasma concentrations of insulin and the glucagon-inhibiting hormone glucagon-like peptide 1 (GLP-1). OBJECTIVE: To investigate whether RYGB-induced hyperglucagonemia may be derived from the gut. DESIGN AND SETTING: Substudy of a prospective cross-sectional study at a university hospital in Copenhagen, Denmark. PARTICIPANTS: Morbidly obese individuals undergoing RYGB (n = 8) with or without type 2 diabetes. INTERVENTIONS: Three months before and after RYGB, participants underwent upper enteroscopy with retrieval of gastrointestinal mucosal biopsy specimens. Mixed-meal tests were performed 1 week and 3 months before and after RYGB. MAIN OUTCOME MEASURES: The 29-amino acid glucagon concentrations in plasma and in mucosal gastrointestinal biopsy specimens were assessed using mass spectrometry-validated immunoassays, and a new monoclonal antibody reacting with immunoreactive glucagon was used for immunohistochemistry. RESULTS: Postprandial plasma concentrations of glucagon after RYGB were increased. Expression of the glucagon gene in the small intestine increased after surgery. Glucagon was identified in the small-intestine biopsy specimens obtained after, but not before, RYGB. Immunohistochemically, mucosal biopsy specimens from the small intestine harbored cells costained for GLP-1 and immunoreactive glucagon. CONCLUSION: Increased concentrations of glucagon were observed in small-intestine biopsy specimens and postprandially in plasma after RYGB. The small intestine harbored cells immunohistochemically costaining for GLP-1 and glucagon-like immunoreactivity after RYGB. Glucagon derived from small-intestine enteroendocrine l cells may contribute to postprandial plasma concentrations of glucagon after RYGB.


Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Derivação Gástrica/métodos , Peptídeo 1 Semelhante ao Glucagon/sangue , Glucagon/sangue , Insulina/sangue , Intestinos/fisiologia , Obesidade Mórbida/sangue , Adolescente , Adulto , Enteroscopia de Balão , Biomarcadores/sangue , Glicemia/análise , Estudos de Casos e Controles , Estudos Transversais , Feminino , Seguimentos , Polipeptídeo Inibidor Gástrico/sangue , Hemoglobina A Glicada/análise , Humanos , Masculino , Refeições , Pessoa de Meia-Idade , Obesidade Mórbida/complicações , Obesidade Mórbida/cirurgia , Período Pós-Prandial , Prognóstico , Estudos Prospectivos , Adulto Jovem
17.
Sci Rep ; 9(1): 9989, 2019 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-31292496

RESUMO

C-peptide, insulin, leptin, and other metabolic hormones are assumed to play roles in breast cancer development; though, results are inconsistent. In this prospective case-control study nested within the Mano a Mano Cohort Study, we assessed the risk of breast cancer with regard to plasma levels of c-peptide, gastric inhibitory polypeptide, insulin, leptin, monocyte chemoattractant protein-1, pancreatic polypeptide, and peptide YY. Among women followed for a median of 8.5 years, 109 breast cancer cases were identified and frequency-matched to 327 controls at a ratio of 1:3. Overall, only c-peptide was observed significantly associated with breast cancer risk. High c-peptide levels (≥ the median level of controls) were significantly associated with increased breast cancer risk (odds ratio [OR] = 1.39, 95% confidence interval [CI]: 1.01, 2.44). In an analysis of participants stratified by age, the significant association between c-peptide levels and breast cancer risk was evident in only women age ≥51 years (OR = 1.53, 95% CI: 1.02, 3.27). Among women age <51 years, high leptin levels were significantly associated with decreased breast cancer risk (OR = 0.49, 95% CI: 0.24, 0.82). Our findings suggest that selected metabolic hormones are associated with breast cancer development in Mexican American women.


Assuntos
Neoplasias da Mama/epidemiologia , Peptídeo C/sangue , Leptina/sangue , Americanos Mexicanos/estatística & dados numéricos , Fatores Etários , Neoplasias da Mama/sangue , Estudos de Casos e Controles , Quimiocina CCL2/sangue , Feminino , Polipeptídeo Inibidor Gástrico/sangue , Humanos , Insulina/sangue , Polipeptídeo Pancreático/sangue , Peptídeo YY/sangue , Estudos Prospectivos , Fatores de Risco , Estados Unidos/epidemiologia , Regulação para Cima
18.
Medicine (Baltimore) ; 98(23): e15965, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31169725

RESUMO

BACKGROUND: Acid exposure time (AET) prolongation plays an important role in the pathogenesis of gastroesophageal reflux disease (GERD). Gastric inhibitory polypeptide (GIP) and pancreatic polypeptide (PP) participate in the regulation of gastric acid secretion, blood glucose and lipid levels, and food intake. In this study, we evaluated the serum GIP and PP levels in refractory GERD patients and analyzed their metabolic and motility characteristics. METHODS: Seventy-three refractory GERD patients were enrolled in this study from September 2015 to September 2017. We investigated the clinical characteristics, severity, and duration of GERD symptoms. High-resolution manometry and 24 hours impedance-pH monitoring were performed to assess esophageal motility and reflux parameters. The patients were divided into the AET- group (AET <4.2%) and AET+ group (AET >4.2%). GIP and PP levels were determined in all subjects and their associations with other parameters evaluated. RESULTS: Age and GERDQ score were significantly higher (P < .05) and acid reflux and heartburn more frequent in the AET+ group than in the AET- group. The contraction front velocity was increased in the AET- group, while there was no significant difference in the distal contraction integral, peristalsis interruption, distal latency, or resting pressures of the lower and upper esophageal sphincters between the 2 groups (P > .05). The serum levels of GIP (P = .003) and PP (P = .012) were significantly increased in the AET+ group. Increased GIP and PP levels were associated with abnormal upright AET (correlation coefficients 0.307 and 0.233, P = .008 and P = .047). There was a positive correlation between GIP and triglyceride levels (correlation coefficient 0.279, P = .017). CONCLUSION: The serum levels of GIP and PP in refractory GERD patients with prolongation of AET are significantly elevated, mainly in the upright position.


Assuntos
Ácido Gástrico/metabolismo , Polipeptídeo Inibidor Gástrico/sangue , Refluxo Gastroesofágico/sangue , Polipeptídeo Pancreático/sangue , Fatores de Tempo , Idoso , Impedância Elétrica , Monitoramento do pH Esofágico , Esôfago/fisiopatologia , Feminino , Refluxo Gastroesofágico/fisiopatologia , Humanos , Masculino , Manometria , Pessoa de Meia-Idade
19.
Folia Med (Plovdiv) ; 61(1): 76-83, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31237842

RESUMO

BACKGROUND: The glucagon-like peptide-1 (GLP-1) and the glucose- dependent Insulinotropic peptide (GIP) are natural incretin hormones, which are secreted respectively by the L- and K-cells of the intestinal mucosa in response to the physiological gastrointestinal glucose absorption. In patients with type 2 diabetes mellitus, the incretin effect is reduced, whereas the results in type 1 diabetes mellitus (T1DM) are heterogeneous, in some patients normal incretin response is observed. AIM: Comparative analysis of the basal serum levels of the incretin hormones GLP-1 and GIP in patients with type 1 DM and in individuals without carbohydrate disorders. MATERIALS AND METHODS: The study included 27 patients with diagnosed T1DM and a control group of 39 individuals without carbohydrate disorders. All participants in the study were subjected to the following clinical measurements and laboratory tests - height, weight, bioimpedance analysis of body composition, fasting blood sugar (BS 0'), postprandial blood sugar (PPBS), glycated haemoglobin (HbA1c) in T1DM patients, total cholesterol (TC), HDL cholesterol (HDL chol), triglycerides (TG), transaminase (AST and ALT), basal serum levels of GLP-1 and GIP. RESULTS: The serum levels of GIP in the patients with type T1DM were significantly higher, compared to the individuals without carbohydrate disorders (P<0.05), while there was no statistically significant difference in the GLP-1 levels. CONCLUSION: The significantly higher GIP levels and the similar GLP-1 levels in our patients with type 1 DM, compared to the individuals without carbohydrate disorders, support the hypothesis of intact incretin effect in this type of diabetes mellitus Key Words: Glucagon-like peptide-1, Glucose-dependent insulinotropic peptide, Type 1 diabetes mellitus.


Assuntos
Diabetes Mellitus Tipo 1/sangue , Polipeptídeo Inibidor Gástrico/sangue , Peptídeo 1 Semelhante ao Glucagon/sangue , Adulto , Glicemia/análise , Feminino , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade
20.
Am J Physiol Endocrinol Metab ; 317(2): E244-E249, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31112407

RESUMO

It is unknown whether activation of hepato-portal vein (PV) glucose sensors plays a role in incretin hormone amplification of oral glucose-stimulated insulin secretion (GSIS). In previous studies, PV glucose infusion increased GSIS through unknown mechanisms, perhaps neural stimulation of pancreatic ß-cells and/or stimulation of gut incretin hormone release. Thus, there could be a difference in the incretin effect when comparing GSIS with portal rather than leg vein (LV) glucose infusion. Plasma insulin and incretin hormones were studied in six overnight-fasted dogs. An oral glucose tolerance test (OGTT) was administered, and then 1 and 2 wk later the arterial plasma glucose profile from the OGTT was mimicked by infusing glucose into either the PV or a LV. The arterial glucose levels were nearly identical between groups (AUCs within 1% of each other). Oral glucose administration increased arterial GLP-1 and GIP levels by more than sixfold, whereas they were not elevated by PV or LV glucose infusion. Oral glucose delivery was associated with only a small incretin effect (arterial insulin and C-peptide were 21 ± 23 and 24 ± 17% greater, respectively, during the 1st hour with oral compared with PV glucose and 14 ± 37 and 13 ± 35% greater, respectively, in oral versus LV; PV versus LV responses were not significantly different from each other). Thus, following an OGTT incretin hormone release did not depend on activation of PV glucose sensors, and the insulin response was not greater with PV compared with LV glucose infusion in the dog. The small incretin effect points to species peculiarities, which is perhaps related to diet.


Assuntos
Glucose/farmacologia , Incretinas/metabolismo , Veia Porta/metabolismo , Animais , Glicemia/análise , Peptídeo C/sangue , Cães , Feminino , Polipeptídeo Inibidor Gástrico/sangue , Peptídeo 1 Semelhante ao Glucagon/sangue , Glucose/administração & dosagem , Teste de Tolerância a Glucose , Membro Posterior/irrigação sanguínea , Infusões Intravenosas , Insulina/sangue , Insulina/metabolismo , Masculino , Veia Porta/química , Fluxo Sanguíneo Regional , Veias
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