Preserved Inhibitory Potency of GLP-1 on Glucagon Secretion in Type 2 Diabetes Mellitus

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.

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Possible applications of gliptins (dipeptidyl peptidase-4 inhibitors) in patients with type 2 diabetes mellitus on the various modes of insulin therapy

Diabetes Mellitus ◽

10.14341/dm7624 ◽

2015 ◽

Vol 18 (4) ◽

pp. 87-91 ◽

Cited By ~ 1

Author(s):

Gagik Radikovich Galstyan ◽

Svetlana Viktorovna Sergeeva

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Glycemic Control ◽

Insulin Therapy ◽

Glucagon Secretion ◽

Insulin Requirement ◽

Dipeptidyl Peptidase 4 ◽

Dipeptidyl Peptidase 4 Inhibitors

The evidence for DPP-4 inhibitors effectiveness at the late stages of type 2 diabetes mellitus (T2DM) are still growing. This is particularly important for those patients who receive insulin without adequately glycemic control. This publication provides the overview of studies which demonstrate high efficacy of Vildagliptin in reducing the blood glucose level in patients with hight duration of T2DM and insulin therapy. DPP-4 inhibitors normalize basal and postprandial glucagon secretion with pancreas α-cells that helps to provide better glycemic control and to reduce a risk of hypoglycemia. Besides, there are very interesting data for Vildagliptin to reduce insulin requirement in T2DM patients in addition to HbA1clevel decrease.

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Mitochondrial Dysfunction in Pancreatic Alpha and Beta Cells Associated with Type 2 Diabetes Mellitus

Life ◽

10.3390/life10120348 ◽

2020 ◽

Vol 10 (12) ◽

pp. 348

Author(s):

Vladimir Grubelnik ◽

Jan Zmazek ◽

Rene Markovič ◽

Marko Gosak ◽

Marko Marhl

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Mitochondrial Dysfunction ◽

Beta Cells ◽

Metabolic Diseases ◽

Hormone Secretion ◽

Glucagon Secretion ◽

Mitochondrial Energy Metabolism

Type 2 diabetes mellitus is a complex multifactorial disease of epidemic proportions. It involves genetic and lifestyle factors that lead to dysregulations in hormone secretion and metabolic homeostasis. Accumulating evidence indicates that altered mitochondrial structure, function, and particularly bioenergetics of cells in different tissues have a central role in the pathogenesis of type 2 diabetes mellitus. In the present study, we explore how mitochondrial dysfunction impairs the coupling between metabolism and exocytosis in the pancreatic alpha and beta cells. We demonstrate that reduced mitochondrial ATP production is linked with the observed defects in insulin and glucagon secretion by utilizing computational modeling approach. Specifically, a 30–40% reduction in alpha cells’ mitochondrial function leads to a pathological shift of glucagon secretion, characterized by oversecretion at high glucose concentrations and insufficient secretion in hypoglycemia. In beta cells, the impaired mitochondrial energy metabolism is accompanied by reduced insulin secretion at all glucose levels, but the differences, compared to a normal beta cell, are the most pronounced in hyperglycemia. These findings improve our understanding of metabolic pathways and mitochondrial bioenergetics in the pathology of type 2 diabetes mellitus and might help drive the development of innovative therapies to treat various metabolic diseases.

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Incretin-Based Antidiabetic Agents: A New Option for Type-2 Diabetes Mellitus

Faridpur Medical College Journal ◽

10.3329/fmcj.v6i1.7412 ◽

1970 ◽

Vol 6 (1) ◽

pp. 51-54

Author(s):

F Ahammad ◽

MAR Howlader ◽

RC Barnab ◽

MY Ali ◽

S Naher ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Complex Disease ◽

Vascular Dysfunction ◽

Glucagon Secretion ◽

Dipeptidyl Peptidase 4 ◽

Glucagon Like Peptide 1 ◽

Microvascular And Macrovascular Complications

Type 2 Diabetes Mellitus (T2DM) is a complex disease with the co-existence of several pathophysiological abnormalities. Both microvascular and macrovascular complications are the main causes of morbidity and mortality, which develops due to endothelial dysfunction. Upregulation of reactive oxygen species, chronic inflammatory and hypercoagulable states are the pathologic basis of vascular dysfunctions in T2DM. To overcome all these abnormalities, different classes of antihyperglycaemic agents have developed. Unfortunately none is able to show satisfactory glycaemic control and to modulate vascular dysfunction. Incretin hormones are secreted from intestine during meal, which enhance insulin secretion and inhibit glucagon secretion from the pancreas. The incretin effect is severely reduced or absent in T2DM. Incretin-based new antidiabetics, both Dipeptidyl Peptidase-4 (DPP-4) inhibitors (Saxagliptin, Sitagliptin, Vildagliptin) and Glucagon Like Peptide-1 (GLP-1) analogs (Exenatide) are now being used globally. They are almost equally effective as conventional antidiabetics like Sulphonylureas (SU), Metformin (MET), Thiazolidinediones (TZD) and insulin when given as monotherapy or combined with SU, MET or TZD as second line agent. Incretin-based agents do not cause hypoglycaemia, produce weight loss in spite of weight gain and do not retain salt or water and almost no gastrointestinal (GIT) symptoms. The agents correct vascular dysfunctions and dyslipidaemia and can be given in elderly and renal impaired patients. DOI: 10.3329/fmcj.v6i1.7412 Faridpur Med. Coll. J. 2011;6(1): 51-54

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