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1.
Int Heart J ; 61(4): 776-780, 2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-32684608

RESUMO

The properties of glucose changes in patients with chronic heart failure remain elusive. In the present study, we investigated the sequential changes of interstitial glucose concentrations in patients with chronic heart failure and heart disease who were not undergoing antidiabetic therapy.A glucose monitoring device (FreeStyle Libre Pro) was attached to the backside of an upper arm and the interstitial glucose concentration was monitored every 15 minutes for 1 week. Eleven patients with chronic heart failure (Heart failure (+) ) and 7 patients with chronic heart diseases but not with heart failure (Heart failure (-) ) were enrolled. The average level and peak value of interstitial glucose concentrations, and the duration of hyperglycemia (≥ 140 mg/dL) were not significantly different between Heart failure (+) and Heart failure (-). The duration of hypoglycemia (< 80 mg/dL) was significantly longer and the trough value was significantly lower in Heart failure (+) compared with Heart failure (-). Most of the patients in Heart failure (+) were exposed to a long duration of hypoglycemia from midnight to morning. Importantly, none of the patients who showed hypoglycemia complained of any subjective symptoms during hypoglycemia. Malabsorption may be one of the mechanisms of hypoglycemia.In summary, patients with chronic heart failure are at risk of developing hypoglycemia even if they do not undergo any antidiabetic therapy.


Assuntos
Glicemia/metabolismo , Insuficiência Cardíaca/complicações , Hipoglicemia/etiologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Insuficiência Cardíaca/metabolismo , Humanos , Hipoglicemia/metabolismo , Masculino , Pessoa de Meia-Idade
2.
Diabetes Metab Syndr ; 14(4): 519-520, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32388332

RESUMO

BACKGROUND AND AIMS: Administration of corticosteroids is common in obstetric practice. In this concise review we queried on the effects of corticosteroids in pregnancies complicated by SARS-CoV-2. METHODS: We performed a literature search on PubMed, regarding the use of corticosteroids in patients with SARS-CoV-2 infection, in pregnancies complicated by SARS-CoV-2, as well as their impact on glycemia in pregnant women with or without diabetes. Furthermore, we searched for effects of SARS-CoV-2 and of other coronaviridae on insulin secretion and glycemia. RESULTS: SARS-CoV-2 infection appears to be a risk factor for complications in pregnancy. Corticosteroids may not be recommended for treating SARS-CoV-2 pneumonia but they may be needed for at-risk pregnancies. Corticosteroids in pregnancy have a diabetogenic potential. SARS-CoV-2 and other coronaviridae may have effects on glycemia. CONCLUSIONS: Caution should be exercised while using corticosteroids in pregnant women with COVID-19 requiring preterm delivery.


Assuntos
Corticosteroides/farmacologia , Infecções por Coronavirus/complicações , Diabetes Mellitus/fisiopatologia , Hiperglicemia/patologia , Hipoglicemia/patologia , Pneumonia Viral/complicações , Complicações Infecciosas na Gravidez/patologia , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/patogenicidade , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Feminino , Homeostase , Humanos , Hiperglicemia/etiologia , Hiperglicemia/metabolismo , Hipoglicemia/etiologia , Hipoglicemia/metabolismo , Secreção de Insulina/efeitos dos fármacos , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Gravidez , Complicações Infecciosas na Gravidez/etiologia , Complicações Infecciosas na Gravidez/metabolismo
3.
Expert Opin Pharmacother ; 21(11): 1311-1318, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32267182

RESUMO

INTRODUCTION: Hypoglycemia in diabetes is a common and unresolved complication during diabetes therapy, even life-threatening. Effective and convenient treatment for rescuing severe diabetic hypoglycemia and maintaining euglycemia is in high demand to reduce hypoglycemia-related morbidity and mortality. Dasiglucagon is a novel glucagon analog for diabetic hypoglycemia therapy. AREAS COVERED: This review summarizes the reported studies associated with the pharmacokinetics, pharmacodynamics, safety, and tolerability characteristics, as well as clinical application of dasiglucagon for managing diabetic hypoglycemia. EXPERT OPINION: Dasiglucagon has demonstrated established solubility and stability in an aqueous formulation. Pharmacokinetics studies have shown dasiglucagon to exhibit higher absorption and a longer plasma elimination half-life than traditional reconstituted glucagon. Pharmacodynamic studies have shown that a full dose of 0.6 mg dasiglucagon could efficiently raise blood glucose level (BGL) by ≥20 mg/dL (9-10 min) from baseline following insulin-induced severe hypoglycemia in patients with type 1 diabetes, as well as rapidly increase BGL with small doses under euglycaemic and hypoglycemic conditions. Dasiglucagon is safe and well tolerated with the main adverse effects being nausea and vomiting. Collectively, dasiglucagon may be a promising candidate for severe diabetic hypoglycemic rescue and a continuous glycemic control in diabetic patients.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemia/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Área Sob a Curva , Glicemia/análise , Ensaios Clínicos Fase II como Assunto , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/metabolismo , Relação Dose-Resposta a Droga , Glucagon/sangue , Meia-Vida , Humanos , Hipoglicemia/sangue , Hipoglicemia/metabolismo , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/sangue , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
Diabet Med ; 37(7): 1094-1102, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32333691

RESUMO

The month of Ramadan forms one of the five pillars of the Muslim faith. Adult Muslims are obligated to keep daily fasts from dawn to sunset, with exceptions. This year Ramadan is due to begin on 23 April 2020 and the longest fast in the UK will be approximately 18 hours in length. In addition, due to the often high-calorie meals eaten to break the fast, Ramadan should be seen as a cycle of fasting and feasting. Ramadan fasting can impact those with diabetes, increasing the risk of hypoglycaemia, hyperglycaemia and dehydration. This year, Ramadan will occur during the global COVID-19 pandemic. Reports show that diabetes appears to be a risk factor for more severe disease with COVID-19. In addition, the UK experience has shown diabetes and COVID-19 is associated with dehydration, starvation ketosis, diabetic ketoacidosis and hyperosmolar hyperglycaemic state. This makes fasting in Ramadan particularly challenging for those Muslims with diabetes. Here, we discuss the implications of fasting in Ramadan during the COVID-19 pandemic and make recommendations for those with diabetes who wish to fast.


Assuntos
Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 2/terapia , Jejum/metabolismo , Férias e Feriados , Islamismo , Betacoronavirus , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/metabolismo , Desidratação/epidemiologia , Desidratação/metabolismo , Desidratação/prevenção & controle , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/metabolismo , Cetoacidose Diabética/epidemiologia , Dietoterapia , Gerenciamento Clínico , Jejum/efeitos adversos , Hidratação , Humanos , Hiperglicemia/epidemiologia , Hiperglicemia/metabolismo , Hiperglicemia/prevenção & controle , Coma Hiperglicêmico Hiperosmolar não Cetótico/epidemiologia , Coma Hiperglicêmico Hiperosmolar não Cetótico/metabolismo , Hipoglicemia/epidemiologia , Hipoglicemia/metabolismo , Hipoglicemia/prevenção & controle , Hipoglicemiantes/uso terapêutico , Cetose/epidemiologia , Cetose/metabolismo , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/metabolismo , Medição de Risco , Reino Unido
5.
Am J Physiol Endocrinol Metab ; 318(5): E779-E790, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32208001

RESUMO

Glucagon's effect on hepatic glucose production (HGP), under hyperglycemic conditions, is time dependent such that after an initial burst of HGP, it slowly wanes. It is not known whether this is also the case under hypoglycemic conditions, where an increase in HGP is essential. This question was addressed using adrenalectomized dogs to avoid the confounding effects of other counterregulatory hormones. During the study, infusions of epinephrine and cortisol were given to maintain basal levels. Somatostatin and insulin (800 µU·kg-1·min-1) were infused to induce hypoglycemia. After 30 min, glucagon was infused at a basal rate (1 ng·kg-1·min-1, baGGN group, n = 5 dogs) or a rate eightfold basal (8 ng·kg-1·min-1, hiGGN group, n = 5 dogs) for 4 h. Glucose was infused to match the arterial glucose levels between groups (≈50 mg/dL). Our data showed that glucagon has a biphasic effect on the liver despite hypoglycemia. Hyperglucagonemia stimulated a rapid, transient peak in HGP (4-fold basal production) over ~60 min, which was followed by a slow reduction in HGP to a rate 1.5-fold basal. During the last 2 h of the experiment, hiGGN stimulated glucose production at a rate fivefold greater than baGGN (2.5 vs. 0.5 mg·kg-1·min-1, respectively), indicating a sustained effect of the hormone. Of note, the hypoglycemia-induced rises in norepinephrine and glycerol were smaller in hiGGN compared with the baGGN group despite identical hypoglycemia. This finding suggests that there is reciprocity between glucagon and the sympathetic nervous system such that when glucagon is increased, the sympathetic nervous response to hypoglycemia is downregulated.


Assuntos
Glucagon/farmacocinética , Gluconeogênese/efeitos dos fármacos , Hipoglicemia/metabolismo , Fígado/efeitos dos fármacos , Sistema Nervoso Simpático/efeitos dos fármacos , Adrenalectomia , Animais , Cães , Epinefrina/farmacologia , Feminino , Hidrocortisona/farmacologia , Hipoglicemia/induzido quimicamente , Insulina , Fígado/metabolismo , Masculino , Somatostatina , Sistema Nervoso Simpático/metabolismo
6.
Arch Endocrinol Metab ; 64(1): 82-88, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32187262

RESUMO

Objective The insulin tolerance test (ITT) has been accepted as the gold standard test for assessing the integrity of the growth hormone (GH) - insulin-like growth factor (IGF-1) axis and the hypothalamic-pituitary-adrenal (HPA) axis. The goal of the test is to achieve clinical and biochemical hypoglycemia at a blood glucose level ≤ 40 mg/dL to effectively and correctly assess the HPA and GH-IGF-1 axes. In this study, the GH and cortisol responses of patients who achieved and failed to achieve biochemical hypoglycemia during an ITT were compared. Subjects and methods One hundred thirty-five patients with pituitary disorders were included in the study. Samples for blood glucose levels were obtained after clear symptoms of clinical hypoglycemia developed. The patients were enrolled in the hypoglycemic and nonhypoglycemic groups according to whether their plasma glucose level ≤ 40 mg/dL or > 40 mg/dL during an ITT, and the groups were compared in terms of their GH and cortisol responses. Results The mean age, body mass index and waist circumference of the two patient groups were found to be similar. The mean blood glucose level was significantly lower in the hypoglycemic group than in the nonhypoglycemic group (19.3 and 52.0 mg/dL, respectively). When the two groups were compared in terms of peak cortisol and GH responses, no statistically significant differences were found. Conclusion The data presented suggest that clinically symptomatic hypoglycemia is as effective as biochemically confirmed hypoglycemia during an ITT. Arch Endocrinol Metab. 2020;64(1):82-8.


Assuntos
Teste de Tolerância a Glucose/métodos , Hormônio do Crescimento Humano/sangue , Hidrocortisona/sangue , Hipoglicemia/sangue , Hipoglicemiantes/administração & dosagem , Fator de Crescimento Insulin-Like I/análise , Insulina/administração & dosagem , Adulto , Automonitorização da Glicemia , Feminino , Teste de Tolerância a Glucose/efeitos adversos , Humanos , Hipoglicemia/diagnóstico , Hipoglicemia/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Masculino , Pessoa de Meia-Idade , Sistema Hipófise-Suprarrenal/metabolismo , Estudos Retrospectivos
7.
J Steroid Biochem Mol Biol ; 198: 105575, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31899316

RESUMO

Diabetes mellitus is a chronic and common metabolic disease that seriously endangers human health. Hyperglycemia and long-term metabolic disorders in diabetes will cause damage to the whole body tissues and organs, resulting in serious complications. Nowadays, drugs for treating diabetes on the market has strong side effects, new treatments thus are urgently needed. Natural therapy of natural ingredients is a promising avenue, this is because natural ingredients are safer and they also show strong activity in the treatment of diabetes. Diosgenin is such a very biologically active natural steroidal sapogenin. The research of diosgenin in the treatment of diabetes and its complications has been widely reported. This article reviews the effects of diosgenin through multiple targets and multiple pathways in diabetes and its complications which including diabetic nephropathy, diabetic liver disease, diabetic neuropathy, diabetic vascular disease, diabetic cardiomyopathy, diabetic reproductive dysfunction, and diabetic eye disease.


Assuntos
Complicações do Diabetes/metabolismo , Diabetes Mellitus/metabolismo , Diosgenina/farmacologia , Animais , Apoptose , Feminino , Glicolipídeos/metabolismo , Células Hep G2 , Humanos , Hipoglicemia/metabolismo , Inflamação , Insulina/metabolismo , Resistência à Insulina , Masculino , Camundongos , Estresse Oxidativo , Plantas/química , Coelhos , Ratos , Esteroides/farmacologia
8.
Am J Physiol Endocrinol Metab ; 318(3): E392-E404, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31910030

RESUMO

In adipose, insulin functions to suppress intracellular lipolysis and secretion of nonesterified fatty acid (NEFA) into plasma. We applied glucose and NEFA minimal models (MM) following a frequently sampled intravenous glucose tolerance test (FSIVGTT) to assess glucose-specific and NEFA-specific insulin resistance. We used total NEFA and individual fatty acids in the NEFA MM, comparing the model parameters in metabolic syndrome (MetSyn) subjects (n = 52) with optimally healthy controls (OptHC; n = 14). Results are reported as mean difference (95% confidence interval). Using the glucose MM, MetSyn subjects had lower [-73% (-82, -57)] sensitivity to insulin (Si) and higher [138% (44, 293)] acute insulin response to glucose (AIRg). Using the NEFA MM, MetSyn subjects had lower [-24% (-35, -13)] percent suppression, higher [32% (15, 52)] threshold glucose (gs), and a higher [81% (12, 192)] affinity constant altering NEFA secretion (ϕ). Comparing fatty acids, percent suppression was lower in myristic acid (MA) than in all other fatty acids, and the stearic acid (SA) response was so unique that it did not fit the NEFA MM. MA and SA percent of total were increased at 50 min after glucose injection, whereas oleic acid (OA) and palmitic acid (PA) were decreased (P < 0.05). We conclude that the NEFA MM, as well as the response of individual NEFA fatty acids after a FSIVGTT, differ between OptHC and MetSyn subjects and that the NEFA MM parameters differ between individual fatty acids.


Assuntos
Ácidos Graxos não Esterificados/metabolismo , Hiperglicemia/metabolismo , Hipoglicemia/metabolismo , Resistência à Insulina , Adulto , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Método Duplo-Cego , Feminino , Glucose/farmacologia , Teste de Tolerância a Glucose , Humanos , Secreção de Insulina/efeitos dos fármacos , Lipídeos/sangue , Masculino , Síndrome Metabólica/metabolismo , Pessoa de Meia-Idade
9.
Biochim Biophys Acta Mol Basis Dis ; 1866(1): 165573, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31672551

RESUMO

Mice homozygous for the human GRACILE syndrome mutation (Bcs1lc.A232G) display decreased respiratory chain complex III activity, liver dysfunction, hypoglycemia, rapid loss of white adipose tissue and early death. To assess the underlying mechanism of the lipodystrophy in homozygous mice (Bcs1lp.S78G), these and wild-type control mice were subjected to a short 4-hour fast. The homozygotes had low baseline blood glucose values, but a similar decrease in response to fasting as in wild-type mice, resulting in hypoglycemia in the majority. Despite the already depleted glycogen and increased triacylglycerol content in the mutant livers, the mice responded to fasting by further depletion and increase, respectively. Increased plasma free fatty acids (FAs) upon fasting suggested normal capacity for mobilization of lipids from white adipose tissue into circulation. Strikingly, however, serum glycerol concentration was not increased concomitantly with free FAs, suggesting its rapid uptake into the liver and utilization for fuel or gluconeogenesis in the mutants. The mutant hepatocyte mitochondria were capable of responding to fasting by appropriate morphological changes, as analyzed by electron microscopy, and by increasing respiration. Mutants showed increased hepatic gene expression of major metabolic controllers typically associated with fasting response (Ppargc1a, Fgf21, Cd36) already in the fed state, suggesting a chronic starvation-like metabolic condition. Despite this, the mutant mice responded largely normally to fasting by increasing hepatic respiration and switching to FA utilization, indicating that the mechanisms driving these adaptations are not compromised by the CIII dysfunction. SUMMARY STATEMENT: Bcs1l mutant mice with severe CIII deficiency, energy deprivation and post-weaning lipolysis respond to fasting similarly to wild-type mice, suggesting largely normal systemic lipid mobilization and utilization mechanisms.


Assuntos
Complexo III da Cadeia de Transporte de Elétrons/metabolismo , Jejum/fisiologia , Mobilização Lipídica/fisiologia , Acidose Láctica/metabolismo , Animais , Glicemia/metabolismo , Colestase/metabolismo , Transporte de Elétrons/fisiologia , Feminino , Retardo do Crescimento Fetal/metabolismo , Gluconeogênese/fisiologia , Glicogênio/metabolismo , Hemossiderose/metabolismo , Hepatócitos/metabolismo , Hepatócitos/fisiologia , Homozigoto , Hipoglicemia/metabolismo , Hipoglicemia/fisiopatologia , Fígado/metabolismo , Fígado/fisiologia , Masculino , Erros Inatos do Metabolismo/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Mitocôndrias/fisiologia , Doenças Mitocondriais/congênito , Doenças Mitocondriais/metabolismo , Aminoacidúrias Renais/metabolismo , Triglicerídeos/metabolismo
10.
Adv Neurobiol ; 23: 209-267, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31667811

RESUMO

Most glycogen in cerebral cortex is located in astrocytes, and the importance of glycogenolysis for critical functions, including neurotransmission and memory consolidation, is strongly supported by many studies. However, specific mechanisms through which glycogen sustains essential functions remain to be established by rigorous, quantitative studies. Cerebral cortical glycogen concentrations are in the range of 10-12 µmol/g in carefully-handled animals, and the calculated rate of glycogenolysis (CMRglycogen) during sensory stimulation is approximately 60% that of glucose utilization (CMRglc) by all cells, with lower rates during acute hypoglycemia and exercise to exhaustion. CMRglycogen is at least fourfold higher when the volume fraction of astrocytes is taken into account. Inclusion of glycogen consumed during sensory stimulation in calculation of the oxygen-glucose index (OGI = CMRO2/CMRglc, which has a theoretical maximum of 6 when no other substrates are metabolized) reduces OGI from 5.0 to 2.8. Thus, at least 53% of the carbohydrate is not oxidized, suggesting that glycogen mobilization supports astrocytic glycolysis, not neuronal oxidation of glycogen-derived lactate that would cause OGI to exceed 6. Failure of glycogenolysis to dilute the specific activity of lactate formed from blood-borne [6-14C]glucose indicates compartmentation of glycolytic metabolism of glucose and glycogen and the rapid release from cerebral cortex of glycogen-derived lactate. Together, these findings invalidate the conclusion by others that glycogen-derived lactate is a major fuel for neurons during neurotransmission, memory consolidation, and exercise to exhaustion. Alternative mechanisms, including glucose sparing for neurons, are presented as testable explanations for data interpreted as lactate shuttling.


Assuntos
Astrócitos/metabolismo , Córtex Cerebral/metabolismo , Metabolismo Energético , Glicogenólise , Glicólise , Hipoglicemia/metabolismo , Neurônios/metabolismo , Condicionamento Físico Animal/fisiologia , Animais , Córtex Cerebral/citologia
11.
Drugs ; 79(17): 1877-1884, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31664708

RESUMO

Oral dapagliflozin (Edistride®, Forxiga®) is approved in the EU at a dosage of 5 mg/day as an adjunct to insulin in adults with type 1 diabetes (T1D) and a body mass index (BMI) of ≥ 27 kg/m2, when insulin alone does not provide adequate glycaemic control despite optimal insulin therapy. As a highly selective SGLT2 inhibitor, dapagliflozin decreases plasma glucose levels independently of insulin action and enables glycaemic control improvement without increasing the risks associated with intensive insulin therapy. In the phase III DEPICT-1 and -2 trials, dapagliflozin 5 mg/day as an adjunct to insulin improved glycaemic control and reduced total daily insulin dose and bodyweight relative to placebo in adults with inadequately controlled T1D, including in patients with a BMI of ≥ 27 kg/m2, over 24 weeks of treatment. In extensions of these trials, these improvements were maintained up to 52 weeks. Dapagliflozin was generally well tolerated with a manageable safety profile and a hypoglycaemia profile generally similar to placebo. The incidence of diabetic ketoacidosis with dapagliflozin in patients with a BMI ≥ 27 kg/m2 was less than half that of the overall population who received dapagliflozin. Dapagliflozin is the first SGLT2 inhibitor to be approved for use in T1D and, while further clinical experience in T1D is required to more definitively establish its efficacy and safety profile, it provides a promising adjunctive treatment option for adults with T1D and a BMI of ≥ 27 kg/m2, when insulin alone does not provide adequate glycaemic control despite optimal insulin therapy.


Assuntos
Compostos Benzidrílicos/farmacologia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Glucosídeos/farmacologia , Hipoglicemiantes/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Administração Oral , Compostos Benzidrílicos/administração & dosagem , Índice de Massa Corporal , Diabetes Mellitus Tipo 1/metabolismo , Glucosídeos/administração & dosagem , Humanos , Hipoglicemia/tratamento farmacológico , Hipoglicemia/metabolismo , Hipoglicemiantes/administração & dosagem , Transportador 2 de Glucose-Sódio/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem
12.
Curr Diab Rep ; 19(10): 97, 2019 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-31493043

RESUMO

PURPOSE OF REVIEW: New more stable formulations of glucagon have recently become available, and these provide an opportunity to expand the clinical roles of this hormone in the prevention and management of insulin-induced hypoglycemia. This is applicable in type 1 diabetes, hyperinsulinism, and alimentary hypoglycemia. The aim of this review is to describe these new formulations of glucagon and to provide an overview of current and future therapeutic opportunities that these may provide. RECENT FINDINGS: Four main categories of glucagon formulation have been studied: intranasal glucagon, biochaperone glucagon, dasiglucagon, and non-aqueous soluble glucagon. All four have demonstrated similar glycemic responses to standard glucagon formulations when administered during hypoglycemia. In addition, potential roles of these formulations in the management of congenital hyperinsulinism, alimentary hypoglycemia, and exercise-induced hypoglycemia in type 1 diabetes have been described. As our experience with newer glucagon preparations increases, the role of glucagon is likely to expand beyond the emergency use that this medication has been limited to in the past. The innovations described in this review likely represent early examples of a pending large repertoire of indications for stable glucagon.


Assuntos
Diabetes Mellitus Tipo 1/metabolismo , Glucagon/administração & dosagem , Hormônios/administração & dosagem , Hipoglicemia/metabolismo , Hipoglicemia/prevenção & controle , Glicemia/metabolismo , Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 1/terapia , Exercício Físico , Homeostase , Humanos , Hipoglicemia/sangue , Hipoglicemia/tratamento farmacológico
13.
Neuropeptides ; 77: 101962, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31488323

RESUMO

Hindbrain energy state shapes hypothalamic control of glucostasis. Dorsal vagal complex (DVC) L-lactate deficiency is a potent glucose-stimulatory signal that triggers neuronal transcriptional activation in key hypothalamic metabolic loci. The energy gauge AMPK is activated in DVC metabolic-sensory A2 noradrenergic neurons by hypoglycemia-associated lactoprivation, but sensor reactivity is diminished by antecedent hypoglycemia (AH). Current research addressed the premise that AH alters hindbrain lactoprivic regulation of hypothalamic metabolic transmitter function. AH did not modify reductions in A2 dopamine-beta-hydroxylase and monocarboxylate-2 (MCT2) protein expression elicited by caudal fourth ventricular delivery of the MCT inhibitor alpha-cyano-4-hydroxycinnamic acid (4CIN), but attenuated 4CIN activation of A2 AMPK. 4CIN constraint of hypothalamic norepinephrine (NE) activity was averted by AH in a site-specific manner. 4CIN induction of Fos immunolabeling in hypothalamic arcuate (ARH), ventromedial (VMN), dorsomedial (DMN) and paraventricular (PVN) nuclei and lateral hypothalamic area (LHA) was avoided by AH. AH affected reactivity of select hypothalamic metabolic neurotransmitter/enzyme marker proteins, e.g. ARH neuropeptide Y, VMN glutamate decarboxylase, DMN RFamide-related peptide-1 and -3, and LHA orexin-A profiles to 4CIN, but did not alleviate drug inhibition of ARH proopiomelanocortin. AH prevented 4CIN augmentation of circulating glucagon, but did not alter hyperglycemic or hypocorticosteronemic responses to that treatment. Results identify hindbrain lactate deficiency as a stimulus for glucagon secretion, and imply that habituation of this critical counter-regulatory hormone to recurring hypoglycemia may involve one or more hypothalamic neurotransmitters characterized here by acclimation to this critical sensory stimulus.


Assuntos
Hipoglicemia/metabolismo , Hipotálamo/metabolismo , Neurônios/metabolismo , Rombencéfalo/metabolismo , Animais , Glicemia/metabolismo , Hipoglicemia/induzido quimicamente , Insulina , Masculino , Neuropeptídeo Y/metabolismo , Norepinefrina/metabolismo , Pró-Opiomelanocortina/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Ratos Sprague-Dawley , Ativação Transcricional
14.
Vet Clin Pathol ; 48(3): 429-434, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31280499

RESUMO

A 13-year-old spayed female Pomeranian dog was presented for persistent, severe hypoglycemia (37 mg/dL; reference interval [RI] 75-128 mg/dL). Progressive nonregenerative anemia (hematocrit 23.3%-15.9%; RI 37.0%-55.0%) and severe thrombocytopenia (36 000/µL; RI 200-500 000/µL) were also noted. The serum insulin concentration was low (0.24 ng/mL; RI 0.302-1.277 ng/mL). Computed tomography revealed multiple splenic nodules (1-6 mm in diameter) and several hepatic nodules (7.6, 12 mm in diameter). Ultrasound-guided fine-needle aspiration of the splenic and hepatic nodules revealed low numbers of epithelial cells with mild cellular atypia, suggestive of a metastatic epithelial tumor, but the primary site was unknown at that time. On careful oral examination under general anesthesia, an enlarged right tonsil was noted grossly, and histopathologic examination of the tonsil diagnosed squamous cell carcinoma. Bone marrow aspirates and biopsies of the splenic and hepatic nodules were performed; all samples were diagnosed as metastatic carcinoma on histopathologic examination. No nodules were present in the pancreas, despite careful palpation during exploratory laparotomy. On immunohistochemistry, the neoplastic cells were positive for cytokeratin AE1/3 and insulin-like growth factor (IGF)-I but were negative for chromogranin A, PGP9.5, insulin, and inconclusive for IGF-II. This is the first report of a primary IGF-I-producing squamous cell carcinoma in the tonsil of a dog with metastases to bone marrow, liver, and spleen, resulting in hypoglycemia.


Assuntos
Carcinoma de Células Escamosas/veterinária , Doenças do Cão/metabolismo , Hipoglicemia/etiologia , Fator de Crescimento Insulin-Like I/metabolismo , Neoplasias Tonsilares/veterinária , Animais , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/secundário , Doenças do Cão/diagnóstico por imagem , Cães , Feminino , Hipoglicemia/metabolismo , Neoplasias Tonsilares/complicações , Neoplasias Tonsilares/diagnóstico por imagem , Neoplasias Tonsilares/metabolismo
15.
Diabetes Metab Syndr ; 13(2): 1035-1040, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31336440

RESUMO

AIMS: The study intended to investigate the impact of controlled glycemia on morbidity and estimated 10-year survival (ES-10Y). METHODS: A cross-sectional investigation was conducted at General Penang Hospital, Malaysia. Demographic criteria and laboratory tests of patients were investigated. Controlled glycemia (CG) was recognized as glycated hemoglobin (HbA1c) ≤7% depending on American Diabetes Association guidelines 2018. Charlson Comorbidity Index (CCI) was used to estimate the confounding influence of co-morbidities and predict ES-10Y. Data was managed by IBM-SPSS 23.0. RESULTS: A total of 400 cases categorized to (44.25%) patients with CG, and (55.75%) cases had uncontrolled glycemia (UCG). HbA1c mean in CG and UCG group was (6.8 ±â€¯0.9 vs 9.5 ±â€¯1.6, P-value: 0.001). Fasting blood glucose was (7 ±â€¯2.3 vs. 9.9 ±â€¯4.3, P-value: 0.001) in CG and UCG group. CCI was (3.38 ±â€¯2.38 vs. 4.42 ±â€¯2.70, P-value: 0.001) and, ES-10Y was (62% vs 46.2%, p-value: 0.001) in CG vs. UCG respectively. Spearman test indicates a negative correlation between CG and CCI (r: 0.19, p-value: 0.001). Logistic regression confirmed HbA1c as a significant predictor of CCI (r2: 0.036, P-value: 0.001). CG has a positive correlation with survival (r: 0.16, P-value: 0.001) and logistic regression of survival (r2: 0.26, P-value: 0.001). CONCLUSIONS: More than one-half of the investigated persons had UCG. Controlled HbA1c was associated with lower co-morbidities and higher ES-10Y.


Assuntos
Biomarcadores/análise , Diabetes Mellitus/mortalidade , Hiperglicemia/prevenção & controle , Hipoglicemia/prevenção & controle , Hipoglicemiantes/uso terapêutico , Glicemia/análise , Estudos Transversais , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/fisiopatologia , Feminino , Seguimentos , Hemoglobina A Glicada/análise , Humanos , Hiperglicemia/metabolismo , Hipoglicemia/metabolismo , Masculino , Pessoa de Meia-Idade , Morbidade , Prognóstico , Taxa de Sobrevida
16.
Diabetes Metab Syndr ; 13(2): 1237-1239, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31336470

RESUMO

We are hereby reporting on a woman with type 1 diabetes getting insulin, 4 shots a day, and referring to us for an episode of severe hypoglycemia occurred after vigorously rubbing a lipo-hypertrophy (LH). She had always injected insulin into an abdominal LH area but had never suffered from any hypoglycemic event (Hypo) during the last period. Nevertheless her history included frequent Hypos, mostly mild-to-moderate but sometimes severe and eventually ending into unconsciousness and her glycemic control was poor (HbA1c 8.3%, mean FPG 161 ±â€¯22 mg/dl, mean PPG 218 ±â€¯51 mg/dl, glycemic variability (106 ±â€¯44 mg/dl). In fact, all of a sudden she rubbed vigorously the LH area trying to get rid of the abdominal skin thickening and soon after a severe Hypo occurred causing her to need for emergency medical assistance. When back at home, she corrected her technique and carefully refrained from inject insulin into the LH so that after six months the lesion disappeared, glycemic control improved and no Hypo occurred any more. Based on the recent publication reporting on a woman with a large LH consisting of thickened skin surrounding some fluid containing insulin at concentrations 13 fold those in blood, we hypothesize that such severe depended on massive insulin release from rubbed skin stores into the blood stream.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemia/etiologia , Hipoglicemiantes/efeitos adversos , Reação no Local da Injeção/complicações , Injeções/efeitos adversos , Adulto , Biomarcadores/análise , Glicemia/análise , Feminino , Hemoglobina A Glicada/análise , Humanos , Hipertrofia , Hipoglicemia/metabolismo , Hipoglicemia/patologia , Hipoglicemiantes/administração & dosagem , Prognóstico
17.
Mol Metab ; 27: 11-21, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31279640

RESUMO

OBJECTIVE: The sympathetic nervous system (SNS) is a key regulator of the metabolic and endocrine functions of adipose tissue. Increased SNS outflow promotes fat mobilization, stimulates non-shivering thermogenesis, promotes browning, and inhibits leptin production. Most of these effects are attributed to norepinephrine activation of the Gs-coupled beta adrenergic receptors located on the surface of the adipocytes. Evidence suggests that other adrenergic receptor subtypes, including the Gi-coupled alpha 2 adrenergic receptors might also mediate the SNS effects on adipose tissue. However, the impact of acute stimulation of adipocyte Gs and Gi has never been reported. METHODS: We harness the power of chemogenetics to develop unique mouse models allowing the specific and spatiotemporal stimulation of adipose tissue Gi and Gs signaling. We evaluated the impact of chemogenetic stimulation of these pathways on glucose homeostasis, lipolysis, leptin production, and gene expression. RESULTS: Stimulation of Gs signaling in adipocytes induced rapid and sustained hypoglycemia. These hypoglycemic effects were secondary to increased insulin release, likely consequent to increased lipolysis. Notably, we also observed differences in gene regulation and ex vivo lipolysis in different adipose depots. In contrast, acute stimulation of Gi signaling in adipose tissue did not affect glucose metabolism or lipolysis, but regulated leptin production. CONCLUSION: Our data highlight the significance of adipose Gs signaling in regulating systemic glucose homeostasis. We also found previously unappreciated heterogeneity across adipose depots following acute stimulation. Together, these results highlight the complex interactions of GPCR signaling in adipose tissue and demonstrate the usefulness of chemogenetic technology to better understand adipocyte function.


Assuntos
Adipócitos/metabolismo , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/metabolismo , Subunidades alfa Gs de Proteínas de Ligação ao GTP/metabolismo , Glucose/metabolismo , Hipoglicemia/metabolismo , Animais , Homeostase , Insulina/metabolismo , Leptina/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Receptores Acoplados a Proteínas-G/metabolismo , Transdução de Sinais
18.
Saudi Med J ; 40(7): 669-674, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31287126

RESUMO

OBJECTIVES: To report the genotype-phenotype characteristics, demographic features and clinical outcome of Omani patients with congenital hyperinsulinism (CHI). Methods: We retrospectively analyzed the clinical, biochemical, genotypical, phenotypical characteristics and outcomes of  children with CHI who were presented to the pediatric endocrine team in the Royal Hospital, Muscat, Oman between January 2007 and December 2016. Results: Analysis of 25 patients with CHI genetically revealed homozygous mutation in ABCC8 in 23 (92%) patients and 2 patients (8%) with compound heterozygous mutation in ABCC8. Fifteen (60%) patients underwent subtotal pancreatectomy as medical therapy failed and 2 (8%) patients showed response to medical therapy. Three patients expired during the neonatal period, 2 had cardiomyopathy and sepsis, and one had sepsis and severe metabolic acidosis. Out of the 15 patients who underwent pancreatectomy, 6 developed diabetes mellitus, 6 continued to have hypoglycemia and required medical therapy and one had pancreatic exocrine dysfunction post-pancreatectomy, following up with gastroenterology clinic and was placed on pancreatic enzyme supplements, while 2 patients continued to have hypoglycemia and both had abdominal MRI and 18-F-fluoro-L-DOPA positron emission tomography scan (PET-scan), that showed  persistent of the disease and started on medical therapy. Conclusion:  Mutation in ABCC8 is the most common cause of CHI and reflects the early age of presentation. There is a need for early diagnosis and appropriate therapeutic strategy.


Assuntos
Hiperinsulinismo Congênito/metabolismo , Hipoglicemia/metabolismo , Apneia/etiologia , Apneia/fisiopatologia , Pré-Escolar , Hiperinsulinismo Congênito/genética , Hiperinsulinismo Congênito/fisiopatologia , Hiperinsulinismo Congênito/terapia , Diabetes Mellitus/tratamento farmacológico , Terapia de Reposição de Enzimas , Insuficiência Pancreática Exócrina/tratamento farmacológico , Feminino , Fármacos Gastrointestinais/uso terapêutico , Heterozigoto , Homozigoto , Humanos , Hipoglicemia/complicações , Hipoglicemia/fisiopatologia , Lactente , Recém-Nascido , Letargia/etiologia , Letargia/fisiopatologia , Masculino , Mutação , Octreotida/uso terapêutico , Omã , Pancreatectomia , Peptídeos Cíclicos/uso terapêutico , Complicações Pós-Operatórias/tratamento farmacológico , Estudos Retrospectivos , Convulsões/etiologia , Convulsões/fisiopatologia , Sirolimo/uso terapêutico , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Receptores Sulfonilureia/genética , Resultado do Tratamento
19.
Diabetes Metab Syndr ; 13(3): 1991-1994, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31235125

RESUMO

BACKGROUND AND OBJECTIVE: Hyperglycemia and some disturbance in antioxidant system lead to free radicals production and oxidative stress. Assessment of some products of oxidative stress could be effective in evaluation of diabetic control. This study aimed at evaluation of glycemic control on salivary lipid peroxidation in diabetic patients. METHODS: This case control study has been done on 44 diabetic (type II) and 44 healthy subjects. Un-stimulated saliva was collected and correlation between malondialdehid (MDA) as an end -product of lipid peroxidation and HbA1c was assessed. RESULTS: MDA and HbA1c of diabetic patients were significantly higher than control group. There was a indirect correlation between MDA and glycemic control level. CONCLUSION: Evaluation of salivary MDA levels could be useful in prediction of glycemic control.


Assuntos
Biomarcadores/análise , Diabetes Mellitus Tipo 2/complicações , Hiperglicemia/patologia , Hipoglicemia/patologia , Peroxidação de Lipídeos , Estresse Oxidativo , Saliva/metabolismo , Glicemia/análise , Estudos de Casos e Controles , Feminino , Seguimentos , Hemoglobina A Glicada/análise , Humanos , Hiperglicemia/etiologia , Hiperglicemia/metabolismo , Hipoglicemia/etiologia , Hipoglicemia/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico
20.
J Neurophysiol ; 122(2): 721-728, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31242045

RESUMO

Adenosine receptors are widely expressed in the brain, and adenosine is a key bioactive substance for neuroprotection. In this article, we clarify systematically the role of adenosine A1 receptors during a range of timescales and conditions when a significant amount of adenosine is released. Using acute hippocampal slices obtained from mice that were wild type or null mutant for the adenosine A1 receptor, we quantified and characterized the impact of varying durations of experimental ischemia, hypoxia, and hypoglycemia on synaptic transmission in the CA1 subregion. In normal tissue, these three stressors rapidly and markedly reduced synaptic transmission, and only treatment of sufficient duration led to incomplete recovery. In contrast, inactivation of adenosine A1 receptors delayed and/or lessened the reduction in synaptic transmission during all three stressors and reduced the magnitude of the recovery significantly. We reproduced the responses to hypoxia and hypoglycemia by applying an adenosine A1 receptor antagonist, validating the clear effects of genetic receptor inactivation on synaptic transmission. We found activation of adenosine A1 receptor inhibited hippocampal synaptic transmission during the acute phase of ischemia, hypoxia, or hypoglycemia and caused the recovery from synaptic impairment after these three stressors using genetic mutant. These studies quantify the neuroprotective role of the adenosine A1 receptor during a variety of metabolic stresses within the same recording system.NEW & NOTEWORTHY Deprivation of oxygen and/or glucose causes a rapid adenosine A1 receptor-mediated decrease in synaptic transmission in mouse hippocampus. We quantified adenosine A1 receptor-mediated inhibition during and synaptic recovery after ischemia, hypoxia, and hypoglycemia of varying durations using a genetic mutant and confirmed these findings using pharmacology. Overall, using the same recording conditions, we found the acute response and the neuroprotective ability of the adenosine A1 receptor depended on the type and duration of deprivation event.


Assuntos
Região CA1 Hipocampal/metabolismo , Hipoglicemia/metabolismo , Hipóxia/metabolismo , Isquemia/metabolismo , Receptor A1 de Adenosina/fisiologia , Estresse Fisiológico/fisiologia , Transmissão Sináptica/fisiologia , Antagonistas do Receptor A1 de Adenosina/farmacologia , Animais , Região CA1 Hipocampal/efeitos dos fármacos , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Receptor A1 de Adenosina/deficiência , Estresse Fisiológico/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos
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