No abstract available.
Glucagon-Like Peptide 1*

At present, surgery has become one of the treatments for type 2 diabetes, but it is still unclear about the therapeutic mechanism. Many experiments has proved that the anatomical and physiological structure has been altered leading to significant changes related to the secretion of gastrointestinal hormones and neuropeptides. These molecular are related to the metabolism of glucose, functions of islet cells and sensitivity of insulin. Intensive studies of glucagon-like peptide-1 (GLP-1) play an important role in the surgical treatment of diabetes and now it has gained increasing recognition. However, GLP-1 must be combined with GLP-1 receptor (GLP-1R) to execute its function. In this paper we reviewed the role of GLP-1 and its receptor in the mechanism of metabolic surgery.
Diabetes Mellitus, Type 2 ; surgery ; Glucagon-Like Peptide 1 ; Glucagon-Like Peptide-1 Receptor ; Humans ; Receptors, Glucagon

Type 2 diabetes (T2D) has been known as 'bi-hormonal disorder' since decades ago, the role of glucagon from alpha-cell has languished whereas beta-cell taking center stage. Recently, numerous findings indicate that the defects of glucagon secretion get involve with development and exacerbation of hyperglycemia in T2D. Aberrant alpha-cell responses exhibit both fasting and postprandial states: hyperglucagonemia contributes to fasting hyperglycemia caused by inappropriate hepatic glucose production, and to postprandial hyperglycemia owing to blunted alpha-cell suppression. During hypoglycemia, insufficient counter-regulation response is also observed in advanced T2D. Though many debates still remained for exact mechanisms behind the dysregulation of alpha-cell in T2D, it is clear that the blockade of glucagon receptor or suppression of glucagon secretion from alpha-cell would be novel therapeutic targets for control of hyperglycemia. Whereas there have not been remarkable advances in developing new class of drugs, currently available glucagon-like peptide-1 and dipeptidyl peptidase-IV inhibitors could be options for treatment of hyperglucagonemia. In this review, we focus on alpha-cell dysfunction and therapeutic potentials of targeting alpha-cell in T2D.
Diabetes Mellitus, Type 2 ; Fasting ; Glucagon ; Glucagon-Like Peptide 1 ; Glucagon-Secreting Cells ; Glucose ; Hyperglycemia ; Hypoglycemia ; Insulin ; Insulin-Secreting Cells ; Receptors, Glucagon

A 58-year-old Malay female with underlying diabetes mellitus, presented with chronic skin lesions, associated with weight loss and anemia. There were erosive, scaling skin lesions over the extremities, gluteal region and perioral area. Skin biopsy histopathological examination revealed Necrolytic Migratory Erythema (NME). A CT scan of the abdomen revealed a pancreatic neck and body tumor with possible liver metastases. She was successfully treated with subcutaneous somatostatin and underwent distal pancreatectomy with wedge resection of liver nodule.
Glucagonoma ; Necrolytic Migratory Erythema ; Glucagon ; Somatostatin

No abstract available.
Glucagon-Like Peptide 1* ; Thyroid Neoplasms* ; Glucagon-Like Peptide-1 Receptor

No abstract available.
Glucagon-Like Peptide 1* ; Thyroid Neoplasms* ; Glucagon-Like Peptide-1 Receptor

Recently, incretin hormone-based therapies, including glucagon-like peptide-1 (GLP-1) analogues and dipeptidyl peptidase-4 (DPP-4) inhibitors, have become the main therapeutic tools in the hyperglycemia management in patients with type 2 diabetes mellitus. These therapeutic agents could fill an important gap in glycemic control for patients with type 2 diabetes because the incretin response is blunted in type 2 diabetes mellitus. GLP-1 analogues can be classified as exendin-4 backbone (Exenatide, Exenatide LAR and Lixisenatide) and human GLP-1 backbone (Liraglutide, Taspoglutide and Albiglutide). Among these, Exenatide, Exenatide LAR and Liraglutide are currently available. This review will focus on the clinical efficacies of GLP-1 analogues in glycemic control for patients with diabetes.
Diabetes Mellitus, Type 2 ; Glucagon ; Glucagon-Like Peptide 1 ; Humans ; Hyperglycemia ; Incretins ; Peptides ; Venoms ; Liraglutide

Recent advances in incretin biology have led to the development of a new class of oral anti-diabetic drugs. To date, there are two known incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), of which the former is a more important therapeutic target for type 2 diabetes. GLP-1 is secreted by intestinal L-cells in response to oral nutrient intake, and it stimulates insulin secretion and suppresses glucagon secretion in a glucose-dependent manner. However, both GLP-1 and GIP are rapidly degraded by dipeptidyl peptidase-4 (DPP-4), a multifunctional type II transmembrane glycoprotein. Thus, several DPP-4 inhibitors with different pharmacologic features are now available and can be used either as monotherapy or in combination with other anti-diabetic agents for the treatment of type 2 diabetes. In both therapeutic regimens, DPP-4 inhibitors have been shown to reduce hemoglobin A1c levels by approximately 0.5-0.8%. In clinical trials, DPP-4 inhibitors were generally well-tolerated, posed a low risk of hypoglycemia, and did not increase body weight. Despite some reports of a possible increased risk of pancreatitis with GLP-1 receptor agonists and DPP-4 inhibitors, no causal associations have been found. Recent randomized controlled clinical trials have shown that DPP-4 inhibitors did not increase or decrease the rates of major adverse cardiovascular events in patients with type 2 diabetes at high risk of cardiovascular disease, even though this class of anti-diabetic agents had various salutary effects in many studies involving animals or healthy and diabetic humans. Additional studies will be required to resolve these disparate conclusions.
Animals ; Biology ; Body Weight ; Cardiovascular Diseases ; Glucagon ; Glucagon-Like Peptide 1 ; Glucagon-Like Peptide-1 Receptor ; Glycoproteins ; Humans ; Hypoglycemia ; Incretins ; Insulin ; Pancreatitis

Glucagon-like peptide-1 (GLP-1) is a member of the proglucagon incretin family, and GLP-1 receptor agonists (RAs) have been introduced as a new class of antidiabetic medications in the past decade. The benefits of GLP-1 RAs are derived from their pleiotropic effects, which include glucose-dependent insulin secretion, suppressed glucagon secretion, and reduced appetite. Moreover, GLP-1 RAs also exert beneficial roles on multiple organ systems in which the GLP-1 receptors exist, including the cardiovascular system. Cardiovascular effects of GLP-1 RAs have been of great interest since the burden from cardiovascular diseases (CVD) has been unbearably increasing in a diabetic population worldwide, despite strict glycemic control and advanced therapeutic techniques to treat CVD. Preclinical studies have already demonstrated the beneficial effects of GLP-1 on myocardium and vascular endothelium, and many clinical studies evaluating changes in surrogate markers of CVD have suggested potential benefits from the use of GLP-1 RAs. Data from numerous clinical trials primarily evaluating the antihyperglycemic effects of multiple GLP-1 RAs have also revealed that changes in most CVD risk markers reported as secondary outcomes have been in favor of GLP-1 RAs treatment. However, to date, there is only one randomized clinical trial of GLP-1 RAs (the ELIXA study) evaluating major cardiovascular events as their primary outcomes, and in this study, a neutral cardiovascular effect of lixisenatide was observed in high-risk diabetic subjects. Therefore, the results of ongoing CVD outcome trials with the use of GLP-1 RAs should be awaited to elucidate the translation of benefits previously seen in CVD risk marker studies into large clinical trials with primary cardiovascular outcomes.
Appetite ; Biomarkers ; Cardiovascular Diseases ; Cardiovascular System ; Endothelium, Vascular ; Glucagon ; Glucagon-Like Peptide 1* ; Glucagon-Like Peptide-1 Receptor* ; Humans ; Incretins ; Insulin ; Myocardium ; Proglucagon

It is well known that both insulin resistance and decreased insulin secretory capacity are important factors in the pathogenesis of type 2 diabetes mellitus (T2DM). In addition to genetic factors, obesity and lipotoxicity can increase the risk of T2DM. Glucagon-like peptide 1 (GLP-1) receptor agonists are novel antidiabetic drugs with multiple effects. They can stimulate glucose-dependent insulin secretion, inhibit postprandial glucagon release, delay gastric emptying, and induce pancreatic β-cell proliferation. They can also reduce the weight of patients with T2DM and relieve lipotoxicity at the cellular level. Many intracellular targets of GLP-1 have been found, but more remain to be identified. Elucidating these targets could be a basis for developing new potential drugs. My colleagues and I have investigated new targets of GLP-1, with a particular focus on pancreatic β-cell lines and hepatic cell lines. Herein, I summarize the recent work from my laboratory, with profound gratitude for receiving the prestigious 2016 Namgok Award.
Awards and Prizes ; Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; Gastric Emptying ; Glucagon ; Glucagon-Like Peptide 1* ; Glucagon-Like Peptide-1 Receptor ; Hepatocytes* ; Humans ; Hypoglycemic Agents ; Insulin ; Insulin Resistance ; Obesity