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

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

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

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

The glucagon-like peptide-1 receptor agonists (GLP-1RAs) were recommended as a monotherapy or combination therapy with oral hypoglycemic agents or basal insulin in the position statement of the Korean Diabetes Association 2017 for pharmacological therapy. Many randomized clinical trials and systematic reviews report that GLP-1RAs have considerable glucose-lowering effect and lead to weight reduction and low risk of hypoglycemia when used as a monotherapy or combination therapy. The cardiovascular safety of GLP-1RAs has been assessed in several randomized clinical trials and systematic reviews. The results of cardiovascular outcome trials of long-acting GLP-1RAs (liraglutide, semaglutide) demonstrated cardiovascular benefits in subjects with type 2 diabetes mellitus and a high risk of cardiovascular disease. The GLP-1RA may be a choice of therapy when weight control and avoidance of hypoglycemia are important, and patients with high risk of cardiovascular disease might also favor choosing GLP-1RA.
Cardiovascular Diseases ; Diabetes Mellitus, Type 2* ; Glucagon-Like Peptide 1* ; Glucagon-Like Peptide-1 Receptor* ; Humans ; Hypoglycemia ; Hypoglycemic Agents ; Insulin ; Weight Loss

Glucagon-like peptide 1 (GLP-1) is an incretin hormone that is released from enteroendocrine L-cells upon nutrient absorption; it stimulates glucose-dependent insulin secretion from pancreatic betacells. GLP-1 has pleiotropic effects including deceleration of gastric emptying, decreased appetite, and increased satiety. Treatment with GLP-1 receptor agonists (GLP-1RAs) improves glycemic control in patients with type 2 diabetes without increasing the risk of hypoglycemia or weight gain. Current GLP-1RAs can be classified by their structure (exendin-4-based or human GLP-1-based), duration of action, and molecular size. Different GLP-1RAs exhibit different pharmacokinetics and pharmacodynamics. Herein we review the characteristics of available GLP-1RAs and discuss current issues such as insulin combination therapy and anti-obesity effects.
Absorption ; Appetite ; Deceleration ; Diabetes Mellitus, Type 2 ; Gastric Emptying ; Glucagon-Like Peptide 1* ; Humans ; Hypoglycemia ; Incretins ; Insulin ; Obesity ; Pharmacokinetics ; Weight Gain ; Glucagon-Like Peptide-1 Receptor

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) were recommended as a monotherapy or combination therapy with oral hypoglycemic agents or basal insulin in the position statement of the Korean Diabetes Association 2017 for pharmacological therapy, which was a change from the previous guideline that recommended them only as a combination therapy. Many randomized clinical trials and systematic reviews report that GLP-1RAs have considerable glucose-lowering effect and lead to weight reduction and low risk of hypoglycemia when used as a monotherapy or combination therapy. The results of cardiovascular outcome trials of long-acting GLP-1RAs (liraglutide, semaglutide) have demonstrated cardiovascular benefits in subjects with type 2 diabetes mellitus and a high risk of cardiovascular disease. The GLP-1RAs may be a choice of therapy when weight control and avoidance of hypoglycemia are important, and patients with high risk of cardiovascular disease might also favor choosing GLP-1RA.
Cardiovascular Diseases ; Diabetes Mellitus ; Diabetes Mellitus, Type 2* ; Glucagon-Like Peptide 1* ; Glucagon-Like Peptide-1 Receptor* ; Humans ; Hypoglycemia ; Hypoglycemic Agents ; Insulin ; Obesity ; Weight Loss

Weight loss is an important goal in the management of several chronic conditions, including type 2 diabetes mellitus, and pharmacological therapies that aid weight loss are appealing. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) are novel glucose-lowering therapies that have been shown to induce clinically significant reductions in body weight. However, this weight loss may not be attributed solely to fat mass (FM). Given the importance of skeletal muscle and lean body mass (LBM) on cardio-metabolic health and physical function, we reviewed the available literature reporting the effects of GLP-1RAs and SGLT2is on body composition. Results demonstrate that, in most circumstances, the weight loss associated with both therapies predominantly comprises a reduction in FM, although significant heterogeneity exists between studies. In over half of the studies identified, the proportion of LBM reduction ranged between 20% and 50% of total weight lost, which is consistent with diet-induced weight loss and bariatric surgery. No clear differences existed between GLP-1RAs and SGLT2is. Consequently, the loss of LBM and skeletal muscle associated with weight loss induced by GLP-1RAs and SGLT2is warrants attention. Strategies to preserve skeletal muscle and improve physical function, for example through structured exercise, are of great importance.
Bariatric Surgery ; Body Composition ; Body Weight ; Diabetes Mellitus, Type 2 ; Glucagon-Like Peptide 1 ; Glucagon-Like Peptide-1 Receptor ; Humans ; Muscle, Skeletal ; Population Characteristics ; Weight Loss

Non-alcoholic fatty liver disease (NAFLD), one of the most common liver diseases, is caused by the disruption of hepatic lipid homeostasis. It is associated with insulin resistance as seen in type 2 diabetes mellitus. Glucagon-like peptide-1 (GLP-1) is an incretin that increases insulin sensitivity and aids glucose metabolism. In recent in vivo and in vitro studies, GLP-1 presents a novel therapeutic approach against NAFLD by increasing fatty acid oxidation, decreasing lipogenesis, and improving hepatic glucose metabolism. In this report, we provide an overview of the role and mechanism of GLP-1 in relieving NAFLD.
Diabetes Mellitus, Type 2 ; Fatty Liver ; Glucagon-Like Peptide 1 ; Glucose ; Homeostasis ; Incretins ; Insulin Resistance ; Lipogenesis ; Liver Diseases ; Receptors, Glucagon

Type 2 diabetes mellitus (T2DM) is increasing in prevalence worldwide. The complications associated with T2DM result in increased mortality and financial cost for those affected. T2DM has long been known to be associated with insulin resistance in peripheral tissues and a relative degree of insulin deficiency. However, the concept that insulin secretion and insulin sensitivity are not linked through a hyperbolic relationship in T2DM has continuously been demonstrated in many clinical trials. Thus, in order to prevent and treat T2DM, it is necessary to identify the substance(s) that will improve the function and survival of the pancreatic beta-cells in both normal and pathologic conditions, so that production and secretion of insulin can be enhanced. Incretin hormones, such as glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic polypeptide (GIP), have been shown to lower the postprandial and fasting glucose and the glycated hemoglobin levels, suppress the elevated glucagon level, and stimulate glucose-dependent insulin synthesis and secretion. In this report, we will review the biological actions and mechanisms associated with the actions of incretin hormones, GLP-1 and GIP, on beta-cell health and compare the differences between GLP-1 and GIP.
Diabetes Mellitus, Type 2 ; Fasting ; Glucagon ; Glucagon-Like Peptide 1 ; Glucose ; Hemoglobins ; Incretins ; Insulin ; Insulin Resistance ; Prevalence