The prevalence of diabetes is increasing worldwide. Glycemic control has been shown to prevent microvascular complications. Many oral hyperglycemic drugs and insulin are being used in the treatment of diabetes, but the effects of those treatments are suboptimal. The two incretin hormones GLP-1 and GIP are released from L- and K-cells, respectively, in response to nutrient intake. GLP-1 stimulates glucose-dependent insulin release. Recently, incretin hormone-based therapies, including GLP-1 agonists and DPP-4 inhibitors, have been used as new treatment options to control glucose levels in patients with type 2 diabetes mellitus. The purpose of this article is to review the efficacy and safety of GLP-1 agonists in the treatment of type 2 diabetes.
Diabetes Mellitus, Type 2 ; Glucagon-Like Peptide 1* ; Glucose ; Humans ; Incretins ; Insulin ; Prevalence

Artificial sweeteners (AS) are ubiquitous in food and beverage products, yet little is known about their effects on the gastrointestinal (GI) tract, and whether they play a role in the development of GI symptoms, especially in patients with irritable bowel syndrome. Utilizing the PubMed and Embase databases, we conducted a search for articles on individual AS and each of these terms: fermentation, absorption, and GI tract. Standard protocols for a systematic review were followed. At the end of our search, we found a total of 617 eligible papers, 26 of which were included. Overall, there is limited medical literature available on this topic. The 2 main areas on which there is data to suggest that AS affect the GI tract include motility and the gut microbiome, though human data is lacking, and most of the currently available data is derived from in vivo studies. The effect on motility is mainly indirect via increased incretin secretion, though the clinical relevance of this finding is unknown as the downstream effect on motility was not studied. The specific effects of AS on the microbiome have been conflicting and the available studies have been heterogeneous in terms of the population studied and both the AS and doses evaluated. Further research is needed to assess whether AS could be a potential cause of GI symptoms. This is especially pertinent in patients with irritable bowel syndrome, a population in whom dietary interventions are routinely utilized as a management strategy.
Absorption ; Beverages ; Fermentation ; Gastrointestinal Tract ; Humans ; Incretins ; Irritable Bowel Syndrome ; Microbiota ; Sweetening Agents*

Recent advances in understanding insulin secretion, action and signaling have led to the development of new pharmacological agents. Several new emerging drugs and drug classes for the management of diabetes are under development, including the incretin mimetic agents (exenatide, dipeptidyl peptidase 4 inhibitors, and glucagon-like peptide 1 analogues), the amylin analogue pramlintide, the cannabinoid-1 receptor antagonist rimonabant, the mixed peroxisome proliferator-activated receptor agonists muraglitazar and the inhaled insulin preparation Exubera. New drugs and technologic advances being made available will help achieve the goals of treating patients with diabetes to all the appropriate metabolic targets. Longer term studies will help providers weigh the benefits, adverse effects, cost, and unknown long-term risks of these medications.
Dipeptidyl-Peptidase IV Inhibitors ; Glucagon-Like Peptide 1 ; Humans ; Incretins ; Insulin ; Islet Amyloid Polypeptide ; Peroxisomes

Incretin hormones are produced by enteroendocrine cells (EECs) in the intestine in response to ingested nutrient stimuli. The incretin effect is defined as the difference in the insulin secretory response between the oral glucose tolerance test and an isoglycemic intravenous glucose infusion study. The pathophysiology of the decreased incretin effect has been studied as decreased incretin sensitivity and/or β-cell dysfunction per se. Interestingly, robust increases in endogenous incretin secretion have been observed in many types of metabolic/bariatric surgery. Therefore, metabolic/bariatric surgery has been extensively studied for incretin physiology, not only the hormones themselves but also alterations in EECs distribution and genetic expression levels of gut hormones. These efforts have given us an enormous understanding of incretin biology from synthesis to in vivo behavior. Further innovative studies are needed to determine the mechanisms and targets of incretin hormones.
Bariatric Surgery ; Biology ; Enteroendocrine Cells ; European Union ; Glucose ; Glucose Tolerance Test ; Incretins* ; Insulin ; Intestines* ; Physiology

Previously proposed main pathogenic mechanisms for type 2 diabetes mellitus (T2DM) are increased hepatic glucose production, insulin resistance and insulin secretion defect. However, further mechanisms involved in the development of T2DM such as decreased incretin effect, increased glucose reabsorption and neurotransmitter dysfunction have been proposed recently. Based on these findings, various medications for glycemic control in T2DM are developing. In this review article, I will focus on the mechanisms and efficacies of up-coming new diabetes medications.
Diabetes Mellitus, Type 2 ; Glucose ; Incretins ; Insulin ; Insulin Resistance ; Neurotransmitter Agents

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

Sodium glucose cotransporter 2 (SGLT2) inhibitors have recently been introduced as a new class of anti-diabetic agents. In addition to their glycemic action, SGLT2 inhibitors also have a number of non-glycemic effects that may contribute to renal and/or cardiovascular benefits. These include effects on tubuloglomerular feedback in the kidney, body weight, blood pressure, and serum uric acid. Other non-glycemic effects of SGLT2 inhibitors that need to be further studied include the effects on lipid profiles, food intake, and secretion of hormones such as leptin, incretins, and aldosterone. Also, the exact mechanisms of various non-glycemic actions should be further studied. Additionally, SGLT2 inhibitor therapy in combination with other drugs may have beneficial glycemic and non-glycemic effects.
Aldosterone ; Blood Pressure ; Body Weight ; Diabetes Mellitus ; Eating ; Glucose ; Incretins ; Kidney ; Leptin ; Sodium ; Uric Acid

Humans ; Incretins/therapeutic use* ; Diabetes Mellitus, Type 2/drug therapy* ; Hypoglycemic Agents/therapeutic use* ; Risk Assessment

Type 2 diabetes mellitus (T2DM) is a multifactorial disease with a complex and progressive pathogenesis. The two primary mechanisms of T2DM pathogenesis are pancreatic β-cell dysfunction and insulin resistance. Pancreatic β-cell dysfunction is recognized to be a prerequisite for the development of T2DM. Therapeutic modalities that improve β-cell function are considered critical to T2DM management; however, blood glucose control remains a challenge for many patients due to suboptimal treatment efficacy and the progressive nature of T2DM. Incretin-based therapies are now the most frequently prescribed antidiabetic drugs in Korea. Incretin-based therapies are a favorable class of drugs due to their ability to reduce blood glucose by targeting the incretin hormone system and, most notably, their potential to improve pancreatic β-cell function. This review outlines the current understanding of the incretin hormone system in T2DM and summarizes recent updates on the effect of incretin-based therapies on β-cell function and β-cell mass in animals and humans.
Animals ; Blood Glucose ; Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; Humans ; Hypoglycemic Agents ; Incretins ; Insulin Resistance ; Korea ; Treatment Outcome

Glucagon-like peptide-1 (GLP-1) is a gut-derived incretin hormone that increases glucose-stimulated insulin secretion in pancreatic beta-cells. Since mitochondrial function is crucial to insulin secretion, we hypothesized that GLP-1 may increase mitochondrial biogenesis in pancreatic beta-cells. We treated INS-1 rat insulinoma cells with GLP-1 or exendin-4 for 48 hours and measured mitochondrial mass and function. Both GLP-1 and exendin-4 increased mitochondrial mass by approximately 20%. The mitochondria/cytosol ratio was increased from 7.60+/-3.12% to 10.53+/-2.70% by exendin-4. In addition, GLP-1 increased the mitochondrial membrane potential and oxygen consumption. Proliferator-activated receptor-gamma coactivator 1alpha expression was increased approximately 2-fold by GLP-1 treatment. In conclusion, the present study presents evidence for a new mechanism of action by which GLP-1 improves pancreatic beta-cell function via enhanced mitochondrial mass and performance.
Animals ; Diabetes Mellitus ; Glucagon-Like Peptide 1* ; Incretins ; Insulin ; Insulinoma* ; Membrane Potential, Mitochondrial ; Mitochondria ; Organelle Biogenesis* ; Oxygen Consumption ; Rats*