scholarly journals The Change in Glucagon Following Meal Ingestion Is Associated with Glycemic Control, but Not with Incretin, in People with Diabetes

2021 ◽  
Vol 10 (11) ◽  
pp. 2487
Author(s):  
Soyeon Yoo ◽  
Dongkyu Kim ◽  
Gwanpyo Koh
Keyword(s):  
Glycemic Control ◽  
Estimated Glomerular Filtration Rate ◽  
Univariate Analysis ◽  
Glucagon Secretion ◽  
Mixed Meal ◽  
C Peptide ◽  
Glucagon Level ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Meal Ingestion

Background: We aimed to investigate the changes in glucagon levels in people with diabetes after the ingestion of a mixed meal and the correlations of variation in glucagon levels with incretin and clinico-biochemical characteristics. Methods: Glucose, C-peptide, glucagon, intact glucagon-like peptide 1 (iGLP-1), and intact glucose-dependent insulinotropic polypeptide (iGIP) were measured in blood samples collected from 317 people with diabetes before and 30 min after the ingestion of a standard mixed meal. The delta (Δ) is the 30-min value minus the basal value. Results: At 30 min after meal ingestion, the glucagon level showed no difference relative to the basal value, whereas glucose, C-peptide, iGLP-1, and iGIP levels showed a significant increase. In univariate analysis, Δglucagon showed not only a strong correlation with HbA1c but also a significant correlation with fasting glucose, Δglucose, and estimated glomerular filtration rate. However, Δglucagon showed no significant correlations with ΔiGLP-1 and ΔiGIP. In the hierarchical multiple regression analysis, HbA1c was the only variable that continued to show the most significant correlation with Δglucagon. Conclusions: People with diabetes showed no suppression of glucagon secretion after meal ingestion. Patients with poorer glycemic control may show greater increase in postprandial glucagon level, and this does not appear to be mediated by incretin.

scholarly journals Effects of meal and incretins in the regulation of splanchnic blood flow

2017 ◽  
Vol 6 (3) ◽  
pp. 179-187 ◽  
Author(s):  
Jukka Koffert ◽  
Henri Honka ◽  
Jarmo Teuho ◽  
Saila Kauhanen ◽  
Saija Hurme ◽  
...  
Keyword(s):  
Blood Flow ◽  
Glucose Disposal ◽  
Mixed Meal ◽  
Organ Specific ◽  
Randomized Intervention ◽  
Glucose Tolerant ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Randomized Intervention Study ◽  
Meal Ingestion

Objective Meal ingestion is followed by a redistribution of blood flow (BF) within the splanchnic region contributing to nutrient absorption, insulin secretion and glucose disposal, but factors regulating this phenomenon in humans are poorly known. The aim of the present study was to evaluate the organ-specific changes in BF during a mixed-meal and incretin infusions. Design A non-randomized intervention study of 10 healthy adults to study splanchnic BF regulation was performed. Methods Effects of glucose-dependent insulinotrophic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) infusions and mixed-meal were tested in 10 healthy, glucose tolerant subjects using PET-MRI multimodal imaging technology. Intestinal and pancreatic BF and blood volume (BV) were measured with 15O-water and 15O-carbon monoxide, respectively. Results Ingestion of a mixed-meal led to an increase in pancreatic and jejunal BF, whereas duodenal BF was unchanged. Infusion of GIP and GLP-1 reduced BF in the pancreas. However, GIP infusion doubled blood flow in the jejunum with no effect of GLP-1. Conclusion Together, our data suggest that meal ingestion leads to increases in pancreatic BF accompanied by a GIP-mediated increase in jejunal but not duodenal blood flow.

Pharmacotherapy for Type 2 Diabetes Mellitus: What’s Up and Coming in the Glucagon-Like Peptide-1 (GLP-1) Pipeline?

2021 ◽  
pp. 089719002110490
Author(s):  
Mary J. Elder ◽  
Emily J. Ashjian
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Glycemic Control ◽  
Glucagon Secretion ◽  
New Drugs ◽  
Beneficial Effects ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glucagon-like peptide-1 (GLP-1), an incretin hormone, is known to lower glucose levels, suppress glucagon secretion, and slow gastric emptying. These properties make GLP-1 an ideal target in treating type 2 diabetes mellitus (T2DM). There are many FDA-approved GLP-1 agonists on the market today, several of which have demonstrated benefit beyond improving glycemic control. Given the beneficial effects of GLP-1 agonists in patients with T2DM, new drugs are in development that combine the mechanism of action of GLP-1 receptor agonism with novel mechanisms and with drugs that promote GLP-1 secretion. These agents are designed to improve glycemic control and target greater body weight reduction. This article discusses new GLP-1 drugs in the pipeline for the treatment of T2DM.

The glucagon-like peptide-1 metabolite GLP-1-(9–36) amide reduces postprandial glycemia independently of gastric emptying and insulin secretion in humans

2006 ◽  
Vol 290 (6) ◽  
pp. E1118-E1123 ◽  
Author(s):  
Juris J. Meier ◽  
Arnica Gethmann ◽  
Michael A. Nauck ◽  
Oliver Götze ◽  
Frank Schmitz ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Plasma Concentrations ◽  
Glucagon Secretion ◽  
Postprandial Glucose ◽  
Glucose Disposal ◽  
C Peptide ◽  
Postprandial Glycemia ◽  
Insulin And Glucagon Secretion ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glucagon-like peptide 1 (GLP-1) lowers glycemia by modulating gastric emptying and endocrine pancreatic secretion. Rapidly after its secretion, GLP-1-(7–36) amide is degraded to the metabolite GLP-1-(9–36) amide. The effects of GLP-1-(9–36) amide in humans are less well characterized. Fourteen healthy volunteers were studied with intravenous infusion of GLP-1-(7–36) amide, GLP-1-(9–36) amide, or placebo over 390 min. After 30 min, a solid test meal was served, and gastric emptying was assessed. Blood was drawn for GLP-1 (total and intact), glucose, insulin, C-peptide, and glucagon measurements. Administration of GLP-1-(7–36) amide and GLP-1-(9–36) amide significantly raised total GLP-1 plasma levels. Plasma concentrations of intact GLP-1 increased to 21 ± 5 pmol/l during the infusion of GLP-1-(7–36) amide but remained unchanged during GLP-1-(9–36) amide infusion [5 ± 3 pmol/l; P < 0.001 vs. GLP-1-(7–36) amide administration]. GLP-1-(7–36) amide reduced fasting and postprandial glucose concentrations ( P < 0.001) and delayed gastric emptying ( P < 0.001). The GLP-1 metabolite had no influence on insulin or C-peptide concentrations. Glucagon levels were lowered by GLP-1-(7–36) amide but not by GLP-1-(9–36) amide. However, the postprandial rise in glycemia was reduced significantly (by ∼6 mg/dl) by GLP-1-(9–36) amide ( P < 0.05). In contrast, gastric emptying was completely unaffected by the GLP-1 metabolite. The GLP-1 metabolite lowers postprandial glycemia independently of changes in insulin and glucagon secretion or in the rate of gastric emptying. Most likely, this is because of direct effects on glucose disposal. However, the glucose-lowering potential of GLP-1-(9–36) amide appears to be small compared with that of intact GLP-1-(7–36) amide.

scholarly journals Renoprotective Effects of Incretin-Based Therapy in Diabetes Mellitus

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Habib Yaribeygi ◽  
Stephen L. Atkin ◽  
Fabrizio Montecucco ◽  
Tannaz Jamialahmadi ◽  
Amirhossein Sahebkar
Keyword(s):  
Diabetic Nephropathy ◽  
Glycemic Control ◽  
Scientific Evidence ◽  
Glucagon Secretion ◽  
Receptor Agonists ◽  
Beneficial Effects ◽  
Reduce Blood Glucose ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
A Minor

Glucagon-like peptide-1 (GLP-1) receptor agonists are recently discovered antidiabetic drugs with potent hypoglycemic effects. Among different mechanisms of activity, these compounds were shown to reduce blood glucose by suppression of glucagon secretion and stimulation of glucose-dependent insulin secretion. These antidiabetic agents have a minor risk of hypoglycemia and have been suggested as a second-line therapy to be added to metformin treatment to further optimize glycemic control in diabetes. More recently, scientific evidence suggests that GLP-1 receptor agonists may particularly afford protection from diabetic nephropathy through modulation of the molecular pathways involved in renal impairment and so improve renal function. This additional benefit adds further weight for these compounds to become promising drugs not only for glycemic control but also to prevent diabetic complications. In this review, we have updated evidence on the beneficial effects of GLP-1 receptor agonists on diabetic nephropathy and detailed the underlying pathophysiological mechanisms.

scholarly journals The dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist tirzepatide: a novel cardiometabolic therapeutic prospect

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Enrique Z. Fisman ◽  
Alexander Tenenbaum
Keyword(s):  
Receptor Agonist ◽  
Therapeutic Option ◽  
Insulin Response ◽  
Glucagon Secretion ◽  
Long Term Effects ◽  
Glucose Levels ◽  
Lower Glucose ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Gip Receptor

AbstractIncretin hormones are peptides released in the intestine in response to the presence of nutrients in its lumen. The main incretins are glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). GLP-1 stimulates insulin secretion, inhibits glucagon secretion at pancreatic α cells and has also extrapancreatic influences as slowing of gastric emptying which increases the feeling of satiety. GIP is the main incretin hormone in healthy people, causative of most the incretin effects, but the insulin response after GIP secretion in type 2 diabetes mellitus (T2DM) is strongly reduced. Therefore, in the past GIP has been considered an unappealing therapeutic target for T2DM. This conception has been changing during recent years, since it has been reported that resistance to GIP can be reversed and its effectiveness restored by improving glycemic control. This fact paved the way for the development of a GIP receptor agonist-based therapy for T2DM, looking also for the possibility of finding a combined GLP-1/GIP receptor agonist. In this framework, the novel dual GIP and GLP-1 receptor agonist tirzepatide seems to be not just a new antidiabetic medication. Administered as a subcutaneous weekly injection, it is a manifold single pharmacological agent that has the ability to significantly lower glucose levels, as well as improve insulin sensitivity, reduce weight and amend dyslipidemia favorably modifying the lipid profile. Tirzepatide and additional dual GLP-1/GIP receptor agonists that could eventually be developed in the future seem to be a promising furthest advance for the management of several cardiometabolic settings. Obviously, it is too early to be overly hopeful since it is still necessary to determine the long-term effects of these compounds and properly verify the potential cardiovascular benefits. Anyway, we are currently facing a novel and very appealing therapeutic option.

The Physiology of Glucagon-like Peptide 1

2007 ◽  
Vol 87 (4) ◽  
pp. 1409-1439 ◽  
Author(s):  
Jens Juul Holst
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Glucagon Secretion ◽  
Peptide Hormone ◽  
Postprandial Glucose ◽  
Cell Secretion ◽  
Amino Acid Peptide ◽  
Reactive Hypoglycemia ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glucagon-like peptide 1 (GLP-1) is a 30-amino acid peptide hormone produced in the intestinal epithelial endocrine L-cells by differential processing of proglucagon, the gene which is expressed in these cells. The current knowledge regarding regulation of proglucagon gene expression in the gut and in the brain and mechanisms responsible for the posttranslational processing are reviewed. GLP-1 is released in response to meal intake, and the stimuli and molecular mechanisms involved are discussed. GLP-1 is extremely rapidly metabolized and inactivated by the enzyme dipeptidyl peptidase IV even before the hormone has left the gut, raising the possibility that the actions of GLP-1 are transmitted via sensory neurons in the intestine and the liver expressing the GLP-1 receptor. Because of this, it is important to distinguish between measurements of the intact hormone (responsible for endocrine actions) or the sum of the intact hormone and its metabolites, reflecting the total L-cell secretion and therefore also the possible neural actions. The main actions of GLP-1 are to stimulate insulin secretion (i.e., to act as an incretin hormone) and to inhibit glucagon secretion, thereby contributing to limit postprandial glucose excursions. It also inhibits gastrointestinal motility and secretion and thus acts as an enterogastrone and part of the “ileal brake” mechanism. GLP-1 also appears to be a physiological regulator of appetite and food intake. Because of these actions, GLP-1 or GLP-1 receptor agonists are currently being evaluated for the therapy of type 2 diabetes. Decreased secretion of GLP-1 may contribute to the development of obesity, and exaggerated secretion may be responsible for postprandial reactive hypoglycemia.

Molecular docking studies and 2D analyses of DPP-4 inhibitors as candidates in the treatment of diabetes

2015 ◽  
Vol 11 (11) ◽  
pp. 3188-3193 ◽  
Author(s):  
Simone Queiroz Pantaleão ◽  
Vinicius Gonçalves Maltarollo ◽  
Sheila Cruz Araujo ◽  
Jadson Castro Gertrudes ◽  
Kathia Maria Honorio
Keyword(s):  
Molecular Docking ◽  
Glycemic Control ◽  
Gastric Inhibitory Polypeptide ◽  
Docking Studies ◽  
Molecular Docking Studies ◽  
Insulin Levels ◽  
Biological Target ◽  
Treatment Of Diabetes ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

DPP-4 is an important biological target related to the treatment of diabetes since some inhibitors can lead to an increase in the insulin levels and the prolonged activity of glucagon-like peptide-1 and gastric inhibitory polypeptide, being effective in glycemic control.

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