Glucocorticoids suppress GLP-1 secretion: possible contribution to their diabetogenic effects

Evidence indicates that subtle abnormalities in glucocorticoid (GC) plasma concentrations and/or in tissue sensitivity to GCs are important in the metabolic syndrome, and it is generally agreed that GCs induce insulin resistance. In addition, it was recently reported that short-term exposure to GCs reduced the insulinotropic effects of the incretin glucagon-like peptide-1 (GLP-1). However, while defective GLP-1 secretion has been correlated to insulin resistance, potential direct effects of GCs on GLP-1-producing L-cell function in terms of GLP-1 secretion and apoptosis have not been studied in any greater detail. In the present study, we sought to determine if GCs could exert direct effects on GLP-1-producing L-cells in terms of GLP-1 secretion and cell viability. We demonstrate here that the glucocorticoid receptor (GR) is expressed in GLP-1-producing cells, where GR activation in response to dexamethasone induces serum- and glucocorticoid-inducible kinase 1 (SGK1) expression but did not influence preproglucagon expression or cell viability. Further, dexamethasone treatment of enteroendocrine GLUTag cells reduced GLP-1 secretion induced by glucose, 2-deoxy-D-glucose, fructose and potassium, while the secretory response to a phorbol ester was unaltered. Furthermore, in vivo administration of dexamethasone to rats reduced the circulating levels of GLP-1 concurrent with induction of insulin resistance and glucose intolerance. We can conclude that GR activation in GLP-1-produci...
Source: Clinical Science - Category: Biomedical Science Authors: Source Type: research

Related Links:

Publication date: Available online 23 April 2019Source: Diabetes &Metabolic Syndrome: Clinical Research &ReviewsAuthor(s): Azza Khalifa Bin Hussain, Elamin Abdelgadir, Fauzia Rashid, Abeer Al Haj, Puja Thadani, Alaaeldin M.K. BashierAbstractFor more than a century, the high occurrences of coronary and peripheral artery diseases in diabetes mellitus patients has been well recognised; despite that, the ability to improve CV event rates by optimizing glycaemic control has remained elusive. Nevertheless, the last decade has seen several cardiovascular outcome clinical trials (CVOTs) of many antihyperglycemic agents tha...
Source: Diabetes and Metabolic Syndrome: Clinical Research and Reviews - Category: Endocrinology Source Type: research
Conclusions: Bariatric surgery appears to be capable of partially reversing the obesity-related epigenome. The identification of potential epigenetic biomarkers predictive for the success of bariatric surgery may open new doors to personalized therapy for severe obesity. Introduction Obesity is currently a huge healthcare problem, worldwide, and is a risk factor for several diseases such as type 2 diabetes (T2D), cardiovascular disease and cancer (1). As the prevalence of obesity reaches pandemic proportions, this metabolic disease is estimated to become the biggest cause of mortality in the near future (2). In fact,...
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research
ConclusionsThe current era witnessed a gradual shift in the management of these patients with diabetes who elected to fast in Ramadan, despite the variable health-related risks with fasting. Results from available RCTs and observational studies in patients with type 2 diabetes showed lower risk of hypoglycemia, similar or better efficacy for glycemic and weight control with SGLT2 inhibitors, incretin mimetics and the newer insulin analogues compared to Sulfonylurea. Gliclazide is a relatively safer option among all sulfonylurea. Patients requiring insulin did better with insulin analogues, especially the newer premixed for...
Source: Diabetes and Metabolic Syndrome: Clinical Research and Reviews - Category: Endocrinology Source Type: research
ConclusionsThe current era witnessed a gradual shift in the management of these patients with diabetes who elected to fast in Ramadan, despite the variable health-related risks with fasting. Results from available RCTs and observational studies in patients with type 2 diabetes showed lower risk of hypoglycemia, similar or better efficacy for glycemic and weight control with SGLT2 inhibitors, incretin mimetics and the newer insulin analogues compared to Sulfonylurea. Gliclazide is a relatively safer option among all sulfonylurea. Patients requiring insulin did better with insulin analogues, especially the newer premixed for...
Source: Diabetes and Metabolic Syndrome: Clinical Research and Reviews - Category: Endocrinology Source Type: research
Publication date: Available online 10 August 2018Source: Diabetes &Metabolic Syndrome: Clinical Research &ReviewsAuthor(s): Ala'a G. Almagthali, Eman H. Alkhaldi, Afnan S. Alzahrani, Ameera K. Alghamdi, Waleed Y. Alghamdi, Ahmed M. KabelAbstractDipeptidyl peptidase (DPP- 4) inhibitors belong to the oral antidiabetic drugs. They are used for the treatment of Type 2 Diabetes mellitus. DPP-4 is an enzyme which puts down the action of hormone, incretin. Incretins belong to the group of hypoglycaemic gastrointestinal hormones. Some studies show that DPP-4 inhibitors causes cancer and some study show that they have antic...
Source: Diabetes and Metabolic Syndrome: Clinical Research and Reviews - Category: Endocrinology Source Type: research
ConclusionsActivation of Tas2r108 in the gut results in a remodeling of enteroendocrine hormone release and bile acid metabolism that ameliorates multiple features of metabolic syndrome. Targeting extraoral bitter taste receptors may be useful in metabolic disease.
Source: Molecular Metabolism - Category: Endocrinology Source Type: research
Cardiovascular outcome in type 2 diabetes and atrial fibrillation. Herz. 2018 May 02;: Authors: Costard-Jäckle A, Tschöpe D, Meinertz T Abstract Diabetes is an independent risk factor for atrial fibrillation (AF). Frequently, it is part of the metabolic syndrome cluster, which includes obesity and hypertension that are independently associated with AF. The risk appears to be higher with longer duration of diabetes and inadequate glycemic control. Patients with diabetes and AF have a substantially increased risk of death and serious cardiovascular complications compared with those in...
Source: Herz - Category: Cardiology Tags: Herz Source Type: research
Publication date: Available online 31 January 2018 Source:Canadian Journal of Cardiology Author(s): Aditya Khetan, Sanjay Rajagopalan The burden of diabetes is expected to rise from 415 million individuals in 2015 to 642 million individuals by 2040. Most individuals pass through a phase of prediabetes before developing full blown diabetes. Insulin resistance, impaired incretin action and insulin hypersecretion are central to the pathophysiology of prediabetes. Individuals >40 years of age and other high risk individuals should be screened for diabetes with fasting plasma glucose and/or HbA1C. For those diagnosed with p...
Source: Canadian Journal of Cardiology - Category: Cardiology Source Type: research
No proper data on prognosis and management of type-2 diabetic ST elevation myocardial infarction (STEMI) patients with culprit obstructive lesion and multivessel non obstructive coronary stenosis (Mv-NOCS) exi...
Source: Diabetology and Metabolic Syndrome - Category: Endocrinology Authors: Tags: Research Source Type: research
Individuals with type 1 diabetes mellitus (T1DM) lack endogenous insulin production and therefore need administration of exogenous insulin to promote normal glucose utilization and storage and regulate glycogen break-down, gluconeogenesis, lipolysis, and ketogenesis [1]. The long-term insulin therapy, however, leads to the presence of obesity or overweight and even metabolic syndrome in these patients, which drive development of insulin resistance and may lead to a more aggressive β-cell apoptosis [2,3].
Source: Diabetes Research and Clinical Practice - Category: Endocrinology Authors: Source Type: research
More News: Biomedical Science | Dexamethasone | Diabetes | Endocrinology | Incretin Therapy | Insulin | Metabolic Syndrome | Science | Study