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1.
Front Endocrinol (Lausanne) ; 12: 649405, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34220705

RESUMO

The finding that high-dose dexamethasone improves survival in those requiring critical care due to COVID-19 will mean much greater usage of glucocorticoids in the subsequent waves of coronavirus infection. Furthermore, the consistent finding of adverse outcomes from COVID-19 in individuals with obesity, hypertension and diabetes has focussed attention on the metabolic dysfunction that may arise with critical illness. The SARS coronavirus itself may promote relative insulin deficiency, ketogenesis and hyperglycaemia in susceptible individuals. In conjunction with prolonged critical care, these components will promote a catabolic state. Insulin infusion is the mainstay of therapy for treatment of hyperglycaemia in acute illness but what is the effect of insulin on the admixture of glucocorticoids and COVID-19? This article reviews the evidence for the effect of insulin on clinical outcomes and intermediary metabolism in critical illness.


Assuntos
COVID-19/tratamento farmacológico , Glucocorticoides/efeitos adversos , Insulina/uso terapêutico , Doenças Metabólicas/induzido quimicamente , Doenças Metabólicas/prevenção & controle , COVID-19/complicações , Cuidados Críticos/métodos , Estado Terminal/terapia , Dexametasona/efeitos adversos , Dexametasona/uso terapêutico , Complicações do Diabetes/diagnóstico , Complicações do Diabetes/tratamento farmacológico , Complicações do Diabetes/mortalidade , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/mortalidade , Diabetes Mellitus/virologia , Glucocorticoides/uso terapêutico , Humanos , Hiperglicemia/complicações , Hiperglicemia/tratamento farmacológico , Hiperglicemia/mortalidade , Doenças Metabólicas/etiologia , Obesidade/complicações , Obesidade/tratamento farmacológico , Obesidade/mortalidade , SARS-CoV-2/fisiologia , Resultado do Tratamento
2.
Molecules ; 26(11)2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34204938

RESUMO

The aim of the study was to evaluate the influence of vitamin K2 (VK2) supplementation on the sphingolipid metabolism pathway in palmitate-induced insulin resistant hepatocytes. The study was carried out on human hepatocellular carcinoma cells (HepG2) incubated with VK2 and/or palmitic acid (PA). The concentrations of sphingolipids were measured by high-performance liquid chromatography. The expression of enzymes from the sphingolipid pathway was assessed by Western blotting. The same technique was used in order to determine changes in the expression of the proteins from the insulin signaling pathway in the cells. Simultaneous incubation of HepG2 cells with palmitate and VK2 elevated accumulation of sphinganine and ceramide with increased expression of enzymes from the ceramide de novo synthesis pathway. HepG2 treatment with palmitate and VK2 significantly decreased the insulin-stimulated expression ratio of insulin signaling proteins. Moreover, we observed that the presence of PA w VK2 increased fatty acid transport protein 2 expression. Our study showed that VK2 activated the ceramide de novo synthesis pathway, which was confirmed by the increase in enzymes expression. VK2 also intensified fatty acid uptake, ensuring substrates for sphingolipid synthesis through the de novo pathway. Furthermore, increased concentration of sphingolipids, mainly sphinganine, inhibited insulin pathway proteins phosphorylation, increasing insulin resistance development.


Assuntos
Vias Biossintéticas/efeitos dos fármacos , Carcinoma Hepatocelular/metabolismo , Ceramidas/análise , Resistência à Insulina , Neoplasias Hepáticas/metabolismo , Ácido Palmítico/efeitos adversos , Vitamina K 2/farmacologia , Cromatografia Líquida de Alta Pressão , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Insulina/metabolismo , Modelos Biológicos , Fosforilação , Esfingosina/análogos & derivados , Esfingosina/análise , Regulação para Cima
3.
Yi Chuan ; 43(7): 694-703, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34284984

RESUMO

As a potent insulinotrophic hormone, glucagon-like peptide 1 (GLP-1) is mainly secreted by intestinal L cells, which can effectively promote the release of insulin and thus reduce blood glucose. Therefore, GLP-1 and its analogs have a good prospect in the treatment of type 2 diabetes. In this study, we constructed mouse intestinal organoids that overexpress GLP-1 by optimizing the GLP-1 lentivirus infection method. We found that supernatants secreted by the GLP-1 overexpression organoids effectively enhanced glucose tolerance in wild-type and diabetic mouse. Thus, the GLP-1 overexpression organoids built in this study may provide a novel strategy for the treatment of type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Peptídeo 1 Semelhante ao Glucagon , Animais , Glicemia , Diabetes Mellitus Tipo 2/genética , Glucagon , Insulina , Camundongos , Organoides
4.
Int J Mol Sci ; 22(13)2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34206460

RESUMO

Clozapine is widely employed in the treatment of schizophrenia. Compared with that of atypical first-generation antipsychotics, atypical second-generation antipsychotics such as clozapine have less severe side effects and may positively affect obesity and blood glucose level. However, no systematic study of clozapine's adverse metabolic effects-such as changes in kidney and liver function, body weight, glucose and triglyceride levels, and retinopathy-was conducted. This research investigated how clozapine affects weight, the bodily distribution of chromium, liver damage, fatty liver scores, glucose homeostasis, renal impairment, and retinopathy in mice fed a high fat diet (HFD). We discovered that obese mice treated with clozapine gained more weight and had greater kidney, liver, and retroperitoneal and epididymal fat pad masses; higher daily food efficiency; higher serum or hepatic triglyceride, aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, and creatinine levels; and higher hepatic lipid regulation marker expression than did the HFD-fed control mice. Furthermore, the clozapine group mice exhibited insulin resistance, poorer insulin sensitivity, greater glucose intolerance, and less Akt phosphorylation; their GLUT4 expression was lower, they had renal damage, more reactive oxygen species, and IL-1 expression, and, finally, their levels of antioxidative enzymes (superoxide dismutase, glutathione peroxidase, and catalase) were lower. Moreover, clozapine reduced the thickness of retinal cell layers and increased iNOS and NF-κB expression; a net negative chromium balance occurred because more chromium was excreted through urine, and this influenced chromium mobilization, which did not help overcome the hyperglycemia. Our clozapine group had considerably higher fatty liver scores, which was supported by the findings of lowered adiponectin protein levels and increased FASN protein, PNPLA3 protein, FABP4 mRNA, and SREBP1 mRNA levels. We conclude that clozapine can worsen nonalcoholic fatty liver disease, diabetes, and kidney and retinal injury. Therefore, long-term administration of clozapine warrants higher attention.


Assuntos
Cromo/deficiência , Clozapina/farmacologia , Intolerância à Glucose/metabolismo , Nefropatias/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade/metabolismo , Doenças Retinianas/metabolismo , Adipócitos/metabolismo , Animais , Biomarcadores , Pesos e Medidas Corporais , Modelos Animais de Doenças , Proteínas de Ligação a Ácido Graxo/genética , Imunofluorescência , Expressão Gênica , Regulação da Expressão Gênica , Imuno-Histoquímica , Insulina/metabolismo , Nefropatias/etiologia , Fígado/metabolismo , Camundongos , Camundongos Obesos , Óxido Nítrico Sintase Tipo II , Hepatopatia Gordurosa não Alcoólica/etiologia , Obesidade/complicações , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Doenças Retinianas/etiologia , Proteína de Ligação a Elemento Regulador de Esterol 1/genética
5.
Nutrients ; 13(6)2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34208400

RESUMO

BACKGROUND: Obesity is a state of excess energy storage resulting in body fat accumulation, and postmenopausal obesity is a rising issue. In this study using ovariectomized (OVX) rats, we mimicked low estrogen levels in a postmenopausal state in order to investigate the effects of different amounts and types of dietary fatty acids on body fat accumulation and body lipid metabolism. METHODS: At 9 weeks of age, rats (n = 40) were given an ovariectomy, eight of which were sham-operated to serve as a control group (S). We then divided OVX rats into four different intervention groups: diet with 5% soybean oil (C), and diet with 5% (L), 15% (M), and 20% (H) (w/w) experimental oil, containing 60% monounsaturated fatty acids (MUFAs) and with a polyunsaturated/saturated fatty acid (P/S) ratio of 5. RESULTS: After OVX, compared to the S group, the C group showed significantly higher body weight, and insulin and leptin levels. Compared to the C group, the H group had lower hepatic triglyceride level and FAS enzyme activity, and higher hepatic ACO and CPT-1 gene expressions and enzyme activities. CONCLUSIONS: An OVX leads to severe weight gain and lipid metabolism abnormalities, while according to previous studies, high fat diet may worsen the situation. However, during our experiment, we discovered that the experimental oil mixture with 60% MUFAs and P/S = 5 may ameliorate these imbalances.


Assuntos
Tecido Adiposo , Gorduras Insaturadas na Dieta/administração & dosagem , Gorduras na Dieta/administração & dosagem , Ácidos Graxos Insaturados/administração & dosagem , Ácidos Graxos/administração & dosagem , Metabolismo dos Lipídeos , Animais , Dieta com Restrição de Gorduras , Dieta Hiperlipídica , Ácido Graxo Sintases/metabolismo , Ácidos Graxos Monoinsaturados/administração & dosagem , Feminino , Insulina/sangue , Leptina/sangue , Fígado/metabolismo , Ovariectomia , Ratos , Ratos Sprague-Dawley , Óleo de Soja/administração & dosagem , Triglicerídeos/metabolismo , Ganho de Peso
6.
Sci Transl Med ; 13(600)2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34193609

RESUMO

The paired box 6 (PAX6) transcription factor is crucial for normal pancreatic islet development and function. Heterozygous mutations of PAX6 are associated with impaired insulin secretion and early-onset diabetes mellitus in humans. However, the molecular mechanism of PAX6 in controlling insulin secretion in human beta cells and its pathophysiological role in type 2 diabetes (T2D) remain ambiguous. We investigated the molecular pathway of PAX6 in the regulation of insulin secretion and the potential therapeutic value of PAX6 in T2D by using human pancreatic beta cell line EndoC-ßH1, the db/db mouse model, and primary human pancreatic islets. Through loss- and gain-of-function approaches, we uncovered a mechanism by which PAX6 modulates glucose-stimulated insulin secretion (GSIS) through a cAMP response element-binding protein (CREB)/Munc18-1/2 pathway. Moreover, under diabetic conditions, beta cells and pancreatic islets displayed dampened PAX6/CREB/Munc18-1/2 pathway activity and impaired GSIS, which were reversed by PAX6 replenishment. Adeno-associated virus-mediated PAX6 overexpression in db/db mouse pancreatic beta cells led to a sustained amelioration of glycemic perturbation in vivo but did not affect insulin resistance. Our study highlights the pathophysiological role of PAX6 in T2D-associated beta cell dysfunction in humans and suggests the potential of PAX6 gene transfer in preserving and restoring beta cell function.


Assuntos
Diabetes Mellitus Tipo 2 , Células Secretoras de Insulina , Ilhotas Pancreáticas , Diabetes Mellitus Tipo 2/metabolismo , Glucose/metabolismo , Homeostase , Humanos , Insulina/metabolismo , Secreção de Insulina , Células Secretoras de Insulina/metabolismo , Ilhotas Pancreáticas/metabolismo
7.
Adv Mind Body Med ; 35(3): 31-39, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34237027

RESUMO

Context: Diabetes is a metabolic disease, with high mortality, and is characterized by increased glucose levels in the blood occurring due to poor pancreatic insulin secretion or development of insulin resistance in the body. Type 2 DM (T2DM) represents 90% of diabetic cases, and its pathogenesis involves a genetic correlation with insulin resistance, ß-cell dysfunction, lifestyle, and environmental factors. Objective: The current study intended to examine the pathophysiology of T2DM, including factors influencing insulin resistance and beta (ß)-cell dysfunction as well as the genetic factors that indicate susceptibility to T2DM. Design: The research team performed a narrative review by searching the Mendeley, Science Direct, Medline, PubMed, Google Scholar, and Springer databases. The search used the keywords Diabetes, insulin secretion and environmental factor. Setting: This study was take place in School of Pharmacy, Suresh Gyan Vihar University, Jaipur, India. Results: The paraoxonase-1 gene Q192R and the L55M, INS-VNTR, and IL-38 gene alterations can result in insulin resistance while PAM variants and miR-132 and miR-18 expression can lead to ß-cell dysfunction. Palmitate-like FFA expression of mRNA MafA, and IRS-2 can lead to impairment of insulin secretion. Conclusions: T2DM is the most common metabolic disorder of the twenty-first century, and its incidence, complications, and morbidity increase every day. The examination of T2DM's pathophysiology and the literature review have revealed that it has a strong correlation with genetic defects.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Diabetes Mellitus Tipo 2/genética , Expressão Gênica , Humanos , Índia , Insulina , Resistência à Insulina/genética , Interleucinas
8.
BMC Health Serv Res ; 21(1): 669, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34238287

RESUMO

BACKGROUND: The aim of this study was to determine how clusters or subgroups of insulin-treated people with diabetes, based upon healthcare resource utilization, select social demographic and clinical characteristics, and diabetes management parameters, are related to health outcomes including acute care visits and hospital admissions. METHODS: This was a non-experimental, retrospective cluster analysis. We utilized Aetna administrative claims data to identify insulin-using people with diabetes with service dates from 01 January 2015 to 30 June 2018. The study included adults over the age of 18 years who had a diagnosis of type 1 (T1DM) or type 2 diabetes mellitus (T2DM) on insulin therapy and had Aetna medical and pharmacy coverage for at least 18 months (6 months prior and 12 months after their index date, defined as either their first insulin prescription fill date or their earliest date allowing for 6 months' prior coverage). We used K-means clustering methods to identify relevant subgroups of people with diabetes based on 13 primary outcome variables. RESULTS: A total of 100,650 insulin-using people with diabetes were identified in the Aetna administrative claims database and met study criteria, including 11,826 (11.7%) with T1DM and 88,824 (88.3%) with T2DM. Of these 79,053 (78.5%) people were existing insulin users. Seven distinct clusters were identified with different characteristics and potential risks of diabetes complications. Overall, clusters were significantly associated with differences in healthcare utilization (emergency room visits, inpatient admissions, and total inpatient days) after multivariable adjustment. CONCLUSIONS: This analysis of healthcare claims data using clustering methodologies identified meaningful subgroups of patients with diabetes using insulin. The subgroups differed in comorbidity burden, healthcare utilization, and demographic factors which could be used to identify higher risk patients and/or guide the management and treatment of diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Insulina , Adulto , Análise por Conglomerados , Demografia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Custos de Cuidados de Saúde , Humanos , Insulina/uso terapêutico , Pessoa de Meia-Idade , Estudos Retrospectivos
9.
Int J Mol Sci ; 22(12)2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34203825

RESUMO

Obesity is closely related to insulin resistance and type 2 diabetes genesis. The liver is a key organ to glucose homeostasis since insulin resistance in this organ increases hepatic glucose production (HGP) and fasting hyperglycemia. The protein-tyrosine phosphatase 1B (PTP1B) may dephosphorylate the IR and IRS, contributing to insulin resistance in this organ. Aerobic exercise is a great strategy to increase insulin action in the liver by reducing the PTP1B content. In contrast, no study has shown the direct effects of strength training on the hepatic metabolism of PTP1B. Therefore, this study aims to investigate the effects of short-term strength exercise (STSE) on hepatic insulin sensitivity and PTP1B content in obese mice, regardless of body weight change. To achieve this goal, obese Swiss mice were submitted to a strength exercise protocol lasting 15 days. The results showed that STSE increased Akt phosphorylation in the liver and enhanced the control of HGP during the pyruvate tolerance test. Furthermore, sedentary obese animals increased PTP1B content and decreased IRS-1/2 tyrosine phosphorylation; however, STSE was able to reverse this scenario. Therefore, we conclude that STSE is an important strategy to improve the hepatic insulin sensitivity and HGP by reducing the PTP1B content in the liver of obese mice, regardless of changes in body weight.


Assuntos
Peso Corporal , Resistência à Insulina , Condicionamento Físico Animal , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Adiposidade , Animais , Regulação para Baixo , Glucose/metabolismo , Insulina/metabolismo , Fígado/metabolismo , Camundongos Obesos , Treinamento de Força , Transdução de Sinais
10.
Int J Mol Sci ; 22(12)2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34203830

RESUMO

Insulin is a polypeptide hormone mainly secreted by ß cells in the islets of Langerhans of the pancreas. The hormone potentially coordinates with glucagon to modulate blood glucose levels; insulin acts via an anabolic pathway, while glucagon performs catabolic functions. Insulin regulates glucose levels in the bloodstream and induces glucose storage in the liver, muscles, and adipose tissue, resulting in overall weight gain. The modulation of a wide range of physiological processes by insulin makes its synthesis and levels critical in the onset and progression of several chronic diseases. Although clinical and basic research has made significant progress in understanding the role of insulin in several pathophysiological processes, many aspects of these functions have yet to be elucidated. This review provides an update on insulin secretion and regulation, and its physiological roles and functions in different organs and cells, and implications to overall health. We cast light on recent advances in insulin-signaling targeted therapies, the protective effects of insulin signaling activators against disease, and recommendations and directions for future research.


Assuntos
Doença , Saúde , Insulina/metabolismo , Animais , Humanos , Secreção de Insulina , Fígado/metabolismo , Transdução de Sinais
11.
BMJ Case Rep ; 14(7)2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34290025

RESUMO

Severe hypertriglyceridaemia can lead to acute pancreatitis, which is associated with maternal and perinatal mortality when it occurs in pregnancy. Rapid reduction of triglyceride levels is a primary goal in the management of severe hypertriglyceridaemia, however, there are limited safe option for treatment in pregnancy. We present a case of a woman without diabetes presenting with severe hypertriglyceridaemia in late gestation who was safely and successfully treated with insulin and review the literature surrounding the management of this important condition.


Assuntos
Diabetes Mellitus , Hipertrigliceridemia , Pancreatite , Doença Aguda , Feminino , Humanos , Hipertrigliceridemia/complicações , Hipertrigliceridemia/tratamento farmacológico , Insulina/uso terapêutico , Pancreatite/tratamento farmacológico , Gravidez , Gestantes
12.
Nat Commun ; 12(1): 4178, 2021 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-34234147

RESUMO

Mosaic loss of chromosome Y (LOY) in leukocytes is the most common form of clonal mosaicism, caused by dysregulation in cell-cycle and DNA damage response pathways. Previous genetic studies have focussed on identifying common variants associated with LOY, which we now extend to rarer, protein-coding variation using exome sequences from 82,277 male UK Biobank participants. We find that loss of function of two genes-CHEK2 and GIGYF1-reach exome-wide significance. Rare alleles in GIGYF1 have not previously been implicated in any complex trait, but here loss-of-function carriers exhibit six-fold higher susceptibility to LOY (OR = 5.99 [3.04-11.81], p = 1.3 × 10-10). These same alleles are also associated with adverse metabolic health, including higher susceptibility to Type 2 Diabetes (OR = 6.10 [3.51-10.61], p = 1.8 × 10-12), 4 kg higher fat mass (p = 1.3 × 10-4), 2.32 nmol/L lower serum IGF1 levels (p = 1.5 × 10-4) and 4.5 kg lower handgrip strength (p = 4.7 × 10-7) consistent with proposed GIGYF1 enhancement of insulin and IGF-1 receptor signalling. These associations are mirrored by a common variant nearby associated with the expression of GIGYF1. Our observations highlight a potential direct connection between clonal mosaicism and metabolic health.


Assuntos
Proteínas de Transporte/genética , Cromossomos Humanos Y/genética , Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença , Mosaicismo , Adulto , Idoso , Proteínas de Transporte/metabolismo , Estudos de Casos e Controles , Análise Mutacional de DNA , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Estudo de Associação Genômica Ampla , Humanos , Insulina/metabolismo , Leucócitos , Mutação com Perda de Função , Masculino , Pessoa de Meia-Idade , Receptor IGF Tipo 1/metabolismo , Transdução de Sinais/genética , Sequenciamento Completo do Exoma
13.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 46(6): 609-614, 2021 Jun 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34275929

RESUMO

OBJECTIVES: With the increase of people's living standards increasing year by year, Type 2 diabetes has brought great economic and living burden to the society and patients. Bariatric surgery can improve metabolic indicators in patients with diabetes, but specific mechanisms are still under study. This study aims to evaluate the effect of Roux-en-Y gastric bypass (RYGB) on insulin resistance in patients with Type 2 diabetes by hyperinsulinemic-euglycemic clamp. METHODS: The peripheral glucose uptake (M value) of 40 patients undergoing laparoscopic Roux-en-Y gastric bypass surgery before and 6 months after the operation were analyzed hyperinsulinemic euglycemic clamp. Fasting blood glucose, glycosylated hemoglobin, triglycerides, andlow-density lipoprotein cholesterol levels as well as body mass index were also analyzed. RESULTS: M value of patients after laparoscopic Roux-en-Y gastric bypass was significantly higher than that before the operation, while indexes such as fasting blood glucose, glycosylated hemoglobin, triglycerides, and low-density lipoprotein cholesterol levels as well as body mass index were lower than those before the operation (all P<0.05). CONCLUSIONS: Laparoscopic Roux-en-Y gastric bypass surgery significantly improves insulin resistance in patients with Type 2 diabetes, decreases blood sugar and blood lipid, and can exert a positive effect on the treatment of Type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Derivação Gástrica , Resistência à Insulina , Laparoscopia , Glicemia , Diabetes Mellitus Tipo 2/cirurgia , Técnica Clamp de Glucose , Humanos , Insulina , Resultado do Tratamento
14.
Nutrients ; 13(7)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209561

RESUMO

Obesity is one of the major health problems worldwide. Following healthy dietary patterns can be difficult in some countries due to the lack of availability of certain foods; thus, alternative foods are needed. Our aim was to evaluate the effect of a dietary pattern consisting of fruit, avocado, whole grains, and trout (FAWGT) on postprandial insulinemia and lipemia in obese Colombian subjects. A randomized controlled crossover study was conducted, in which 44 subjects with BMI ≥ 30 kg/m2 followed either a FAWGT diet or a diet high in saturated fat and rich in processed carbohydrates. Levels of lipids and carbohydrates were measured during the postprandial state. The FAWGT diet reduced fasting insulin, VLDL, and HOMA-IR after 8 weeks (p < 0.05), while there was a lower postprandial increase in TG, VLDL, and insulin levels after both acute and chronic intake of FAWGT diet (p < 0.05). The intake of FAWGT-diet was characterized by high consumption of foods rich in fiber, MUFAs, and vitamins C and E (p < 0.05). The consumption of a diet composed of fruit, avocado, whole grains, and trout has emerged as a valid alternative to the foods included in other heart-healthy diets since it improves postprandial lipemia and insulinemia in obese people and has similar beneficial effects to these healthy models.


Assuntos
Dieta Saudável/métodos , Ingestão de Alimentos/fisiologia , Hiperinsulinismo/dietoterapia , Hiperlipidemias/dietoterapia , Obesidade/dietoterapia , Animais , Glicemia/análise , Índice de Massa Corporal , VLDL-Colesterol/sangue , Estudos Cross-Over , Carboidratos da Dieta/administração & dosagem , Gorduras na Dieta/administração & dosagem , Jejum/sangue , Feminino , Frutas , Humanos , Hiperinsulinismo/sangue , Hiperinsulinismo/etiologia , Hiperlipidemias/sangue , Hiperlipidemias/etiologia , Insulina/sangue , Resistência à Insulina , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/complicações , Persea , Período Pós-Prandial/fisiologia , Alimentos Marinhos , Triglicerídeos/sangue , Truta , Grãos Integrais
15.
BMJ Case Rep ; 14(7)2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34301693

RESUMO

We present a case of a 73-year-old woman who developed recurrent hypoglycaemia during a prolonged hospital stay following a mechanical fall. She had a complex history of insulin-treated diabetes mellitus, hypothyroidism, diffuse systemic cutaneous sclerosis, Raynaud's disease, previous breast cancer, Barrett's oesophagus and previous partial gastrectomy for a benign mass. Hypoglycaemia persisted despite weaning of insulin. She had no clinical features of adrenal or pituitary insufficiency with an acceptable cortisol on stopping prednisolone and had an optimal thyroid replacement. A 72-hour fast elicited hypoglycaemia with corresponding low insulin level. Although the C-peptide was detectable, there were no clinical, biochemical or radiological features suggestive of insulinoma. Reactive hypoglycaemia post partial gastrectomy was ruled out based on limited relation of the hypoglycaemia to meals and the low insulin levels. Hydroxychloroquine (HCQ)-induced hypoglycaemia was considered based on previous case reports and the recent literature, with a successful resolution of hypoglycaemia on discontinuation of HCQ.


Assuntos
Diabetes Mellitus Tipo 2 , Hipoglicemia , Neoplasias Pancreáticas , Idoso , Peptídeo C , Feminino , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/tratamento farmacológico , Insulina
16.
BMJ Case Rep ; 14(7)2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34301698

RESUMO

Insulin oedema is a rare complication of insulin treatment characterised by an absence of heart, liver and renal involvement. Insulin oedema typically develops in the lower extremities or, less frequently, as generalised oedema after initiation of insulin therapy. We report a 59-year-old man with poorly controlled type 2 diabetes who developed oedema in his penis and scrotum accompanied by weight gain following intensive insulin therapy. His oedema improved after reduction of the daily insulin injection dose and treatment for urinary retention. Penile and scrotal oedema is a rare physical finding for the patient with diabetes. Therefore, in patients with poorly controlled diabetes who have started insulin therapy, physicians should pay attention to urinary retention and do not miss changes in weight gain or oedema in the lower body, including the perineal region.


Assuntos
Diabetes Mellitus Tipo 2 , Retenção Urinária , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Edema/induzido quimicamente , Humanos , Insulina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pênis , Escroto , Retenção Urinária/induzido quimicamente
17.
Int J Mol Sci ; 22(13)2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34202916

RESUMO

It has been well established that insulin-like growth factors (IGFs) mainly mediate long-term actions in cell fates, whereas insulin predominantly exerts its role on metabolic activity. Indeed, insulin mediates multiple anabolic biological activities in glucose and amino acid transport, lipid and protein synthesis, the induction of glycogen, the inhibition of gluconeogenesis, lipolysis, and protein degradation. The interactions and differences between insulin receptor signaling and IGF-I receptor signaling in the metabolism and the cell fates are quite complicated. Because of the overlapping actions of IGF-I singling with insulin signaling, it has been difficult to distinguish the role of both signaling mechanisms on the metabolism. Furthermore, comprehensive information on the IGF-I function in respective tissues remains insufficient. Therefore, we need to clarify the precise roles of IGF-I signaling on the metabolism separate from those of insulin signaling. This review focuses on the metabolic roles of IGFs in the respective tissues, especially in terms of comparison with those of insulin, by overviewing the metabolic phenotypes of tissue-specific IGF-I and insulin receptor knockout mice, as well as those in mice treated with the dual insulin receptor/IGF-I receptor inhibitor OSI-906.


Assuntos
Metabolismo Energético , Somatomedinas/metabolismo , Animais , Regulação da Expressão Gênica , Humanos , Insulina/metabolismo , Camundongos , Especificidade de Órgãos , Receptor IGF Tipo 1/metabolismo , Receptor de Insulina/metabolismo , Transdução de Sinais , Somatomedinas/genética
18.
Medicina (Kaunas) ; 57(7)2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34209125

RESUMO

Background and Objectives: The daily lifestyle management of diabetes requires accurate predictions of the blood glucose level between meals. The objective of this study was to improve the accuracy achieved by previous work, especially on the mid-term, i.e., 120 to 180 min prediction horizons, for insulin-dependent patients. Materials and Methods: An absorption model-based method is proposed to train an artificial neural network with the bolus and basal insulin dosing and timing, the baseline blood glucose level, the maximal glucose infusion rate, and the total carbohydrate content as parameters. The approach was implemented in various algorithmic setups, and it was validated on data from a small-scale clinical trial with continuous glucose monitoring. Results: Root mean square error results for the mid-term horizons are 1.72 mmol/L (120 min) and 1.95 mmol/L (180 min). The accuracy of the proposed model measured on the clinical data is better than the accuracy reported by any other currently available and comparable models. Conclusions: A relatively short (ca. two weeks) training sample of a continuous glucose monitor and dietary/insulin log is sufficient to provide accurate predictions. For the outpatient application in practice, a hybrid model is proposed that combines the present mid-term method with the authors' previous work for short-term predictions.


Assuntos
Glicemia , Diabetes Mellitus Tipo 1 , Automonitorização da Glicemia , Humanos , Hipoglicemiantes/uso terapêutico , Insulina , Refeições
19.
Biomed Pharmacother ; 139: 111662, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34243629

RESUMO

Metformin is one of the most prescribed drugs in type II diabetes (T2DM) which has recently found new applications in the prevention and treatment of various illnesses, from metabolic disorders to cardiovascular and age-related diseases. Metformin improves insulin resistance (IR) by modulating metabolic mechanisms and mitochondrial biogenesis. Alternation of microRNAs (miRs) in the treatment of IR-related illnesses has been observed by metformin therapy. MiRs are small non-coding RNAs that play important roles in RNA silencing, targeting the 3'untranslated region (3'UTR) of most mRNAs and inhibiting the translation of related proteins. As a result, their dysregulation is associated with many diseases. Metformin may alter miRs levels in the treatment of various diseases by AMPK-dependent or AMPK-independent mechanisms. Here, we summarized the therapeutic role of metformin by modifying the aberrant expression of miRs as potential biomarkers or therapeutic targets in diseases in which IR plays a key role.


Assuntos
Hipoglicemiantes/uso terapêutico , Resistência à Insulina/genética , Resistência à Insulina/fisiologia , Metformina/farmacologia , Metformina/uso terapêutico , MicroRNAs/genética , Animais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Humanos , Hipoglicemiantes/farmacologia , Insulina/genética
20.
Molecules ; 26(13)2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34201708

RESUMO

Caffeine is a plant alkaloid present in food and beverages consumed worldwide. It has high lipid solubility with recognized actions in the central nervous system and in peripheral tissues, notably the adipose depots. However, the literature is scant regarding caffeine's influence on adipocyte functions other than lipolysis, such as glucose incorporation into lipids (lipogenesis) and amine oxidation. The objective of this study was to explore the direct effects of caffeine and of isobutylmethylxanthine (IBMX) on these adipocyte functions. Glucose transport into fat cells freshly isolated from mice, rats, or humans was monitored by determining [3H]-2-deoxyglucose (2-DG) uptake, while the incorporation of radiolabeled glucose into cell lipids was used as an index of lipogenic activity. Oxidation of benzylamine by primary amine oxidase (PrAO) was inhibited by increasing doses of caffeine in human adipose tissue preparations with an inhibition constant (Ki) in the millimolar range. Caffeine inhibited basal and insulin-stimulated glucose transport as well as lipogenesis in rodent adipose cells. The antilipogenic action of caffeine was also observed in adipocytes from mice genetically invalidated for PrAO activity, indicating that PrAO activity was not required for lipogenesis inhibition. These caffeine inhibitory properties were extended to human adipocytes: relative to basal 2-DG uptake, set at 1.0 ± 0.2 for 6 individuals, 0.1 mM caffeine tended to reduce uptake to 0.83 ± 0.08. Insulin increased uptake by 3.86 ± 1.11 fold when tested alone at 100 nM, and by 3.21 ± 0.80 when combined with caffeine. Our results reinforce the recommendation of caffeine's potential in the treatment or prevention of obesity complications.


Assuntos
Adipócitos/efeitos dos fármacos , Aminas Biogênicas/metabolismo , Cafeína/farmacologia , Glucose/metabolismo , Lipogênese/efeitos dos fármacos , Monoaminoxidase/metabolismo , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Benzilaminas/metabolismo , Transporte Biológico/efeitos dos fármacos , Desoxiglucose/metabolismo , Humanos , Insulina/metabolismo , Lipólise/efeitos dos fármacos , Camundongos , Ratos , Xantinas/farmacologia
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