BACKGROUND: We examined the change in the levels of incretin hormone and effects of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) on insulin secretion in women with previous gestational diabetes (pGDM). METHODS: A 75-g oral glucose tolerance test (OGTT) was conducted on 34 women with pGDM. In addition, 11 women with normal glucose tolerance, matched for age, height and weight, were also tested. The insulin, GIP, GLP-1, and glucagon concentrations were measured, and their anthropometric and biochemical markers were also measured. RESULTS: Among 34 women with pGDM, 18 had normal glucose tolerance, 13 had impaired glucose tolerance (IGT) and 1 had diabetes. No significant differences were found in GLP-1 concentration between the pGDM and control group. However, a significantly high level of glucagon was present in the pGDM group at 30 minutes into the OGTT. The GIP concentration was elevated at 30 minutes and 60 minutes in the pGDM group. With the exception of the 30-minute timepoint, women with IGT had significantly high blood glucose from 0 to 120 minutes. However, there was no significant difference in insulin or GLP-1 concentration. The GIP level was significantly high from 0 to 90 minutes in patients diagnosed with IGT. CONCLUSION: GLP-1 secretion does not differ between pGDM patients and normal women. GIP was elevated, but that does not seem to induce in increase in insulin secretion. Therefore, we conclude that other factors such as heredity and environment play important roles in the development of type 2 diabetes.
Biomarkers ; Blood Glucose ; Diabetes, Gestational ; Female ; Glucagon ; Glucagon-Like Peptide 1 ; Glucose ; Glucose Tolerance Test ; Heredity ; Humans ; Incretins ; Insulin ; Pregnancy

The Committee of Clinical Practice Guidelines of the Korean Diabetes Association revised and updated the 6th Clinical Practice Guidelines in 2019. Targets of glycemic, blood pressure, and lipid control in type 2 diabetes mellitus (T2DM) were updated. The obese and overweight population is increasing steadily in Korea, and half of the Koreans with diabetes are obese. Evidence-based recommendations for weight-loss therapy for obesity management as treatment for hyperglycemia in T2DM were provided. In addition, evidence from large clinical studies assessing cardiovascular outcomes following the use of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide 1 receptor agonists in patients with T2DM were incorporated into the recommendations.
Blood Pressure ; Diabetes Mellitus, Type 2 ; Diagnosis ; Glucagon-Like Peptide 1 ; Humans ; Hyperglycemia ; Korea ; Obesity ; Overweight

Glucagon like peptide-1 (GLP-1) is an intestinal L cell derived incretin hormone which stimulates insulin secretion of beta cell and inhibits glucagon secretion of alpha cell of pancreatic islets. GLP-1 receptors are located in pancreas as well as in a wide variety of tissue such as gastrointestinal tract, heart, blood vessel, lung, brain, kidney, and bone. Therefore GLP-1 and GLP-1 based treatment have multiple extrapancreatic effects which are inhibition of gastrointestinal motility, reduction of appetite, weight loss, increase of cardiac output, cardiovascular protection, neuroprotection, renoprotection, and increase of bone mineral density. Recently, besides GLP-1 receptor dependent pathway, GLP-1 receptor independent pathway has been identified in the extrapancreatic effect of GLP-1 in liver, adipose tissue, muscle, cardiovascular system. This review provides an overview of the pleiotropic effect of GLP-1 in the extrapancreatic organ through review of animal and clinical research.
Adipose Tissue ; Animals ; Appetite ; Blood Vessels ; Bone Density ; Brain ; Cardiac Output ; Cardiovascular System ; Enteroendocrine Cells ; Gastrointestinal Motility ; Gastrointestinal Tract ; Glucagon* ; Glucagon-Like Peptide 1 ; Heart ; Incretins ; Insulin ; Islets of Langerhans ; Kidney ; Liver ; Lung ; Pancreas ; Weight Loss ; Glucagon-Like Peptide-1 Receptor

OBJECTIVETo observe postoperative glucose tolerance, gastric inhibitory polypeptide (GIP) , and glucogan-like peptide-1 (GLP-1) in normal glucose level dogs after undergoing gastric bypass procedures, and to explore the mechanism of gastric bypass procedures to treat type 2 diabetes.

METHODSThe 6 dogs with normal glucose tolerance had undergone gastric bypass procedures, and measure preoperative and postoperative oral and intravenous glucose tolerance (at time points 1, 2, and 4 weeks) through changes in blood glucose, insulin, gastric inhibitory polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and measure preoperative and postoperative week 4 pancreatic tissue morphology.

RESULTSSecond weeks after operation, the fasting blood sugar was (3.58 ± 0.33) mmol/L, and significantly lower than preoperative (t = 3.571, P < 0.05). The GLP-1 level before oral glucose tolerance test (OGTT) and 30 minutes after OGTT were (0.90 ± 0.21) and (0.91 ± 0.19) pmol/L respectively, and significantly higher than preoperative (t value were -3.660 and -2.971, P < 0.05). GLP-1 levels began to decrease in the second week after surgery. After 4 weeks, the index recovered to the preoperative level. Four weeks after surgery when compared with preoperative, islet morphology, islet number (6.8 ± 0.8 and 7.1 ± 0.8 respectively) and islet cells (16.7 ± 2.5 and 16.3 ± 3.1 respectively) did not change significantly (P > 0.05).

CONCLUSIONGastric bypass procedures could be briefly affect normal glucose tolerance in dogs' blood glucose, insulin and diabetes-related gastrointestinal hormones.

Animals ; Blood Glucose ; Diabetes Mellitus, Type 2 ; Dogs ; Gastric Bypass ; Gastric Inhibitory Polypeptide ; Glucagon ; Glucagon-Like Peptide 1 ; blood ; Glucose ; Insulin ; blood

BACKGROUNDFood composition and style is changing dramatically now, which causes inappropriate secretion of hormones from brain, gastrointestinal and endo-pancreas, may be related to unbalance of glucose in blood. The aim of this study was to explore the fast response of C-peptide, glucagon-like peptide-1 (GLP-1), ghrelin and endomorphin-1 (EM-1) to the eastern and western style meals in patients with type 2 diabetes mellitus.

METHODSThe study enrolled 57 patients with type 2 diabetes (20 men and 37 women, mean age (67.05 ± 8.26) years). Eastern style meal (meal A) and western style meal (meal B) were designed to produce the fullness effect. C-peptide, GLP-1, ghrelin and EM-1 were assessed before (0 hour) and after (2 hours) each diet.

RESULTSThe delta (2h - 0h) of C- peptide in meal A was significantly lower than that in meal B (P = 0.0004). C-peptide, GLP-1, ghrelin and EM-1 were obviously higher before meal B than those before meal A (P < 0.0001, < 0.0001, = 0.001, = 0.0004 respectively). Blood glucose 2 hours and 3 hours after meal B were higher than those after meal A (P = 0.0005, 0.0079 respectively). Correlations between GLP-1 and ghrelin were strongly positive before both meals and 2 hours after both meals and also in relation to the delta of meal A and meal B (r(A0h) = 0.7836, r(B0h) = 0.9368, r(A2h) = 0.7615, r(B2h) = 0.9409, r(A(2h-0h)) = 0.7531, r((2h-0h))B = 0.9980, respectively, P < 0.0001).

CONCLUSIONWestern style meal (high fat and protein food) could make more response of C-peptide than eastern style meal, and could stimulate more gut hormones (GLP-1, ghrelin) and brain peptide (EM-1) at the first phase of digestion.

Aged ; C-Peptide ; blood ; Diabetes Mellitus, Type 2 ; blood ; Diet ; Fasting ; blood ; Female ; Ghrelin ; blood ; Glucagon-Like Peptide 1 ; blood ; Humans ; Male ; Middle Aged ; Oligopeptides ; blood ; Postprandial Period

In 2018, the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) published a consensus recommendation on management of hyperglycemia. This consensus report emphasized the need for patient-centered management considering multimorbidity and individual patient preferences and barriers. Patients with type 2 diabetes with established atherosclerotic cardiovascular disease who fail to control blood glucose with the initial glucose-lowering medication are recommended a sodium-glucose cotransporter 2 (SGLT2) inhibitor or a glucagon-like peptide 1 (GLP-1) receptor agonist. For patients with chronic kidney disease and heart failure, SGLT2 inhibitors are recommended. In patients who need an injectable medication, GLP-1 receptor agonists are the preferred choice over insulin. In this section, we summarize “Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).”
Atherosclerosis ; Blood Glucose ; Cardiovascular Diseases ; Comorbidity ; Consensus ; Diabetes Mellitus ; Glucagon-Like Peptide 1 ; Glucagon-Like Peptide-1 Receptor ; Heart Failure ; Humans ; Hyperglycemia ; Insulin ; Patient Preference ; Patient-Centered Care ; Renal Insufficiency, Chronic

The incretin hormones glucagon like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) have recently received much attention for their roles in type 2 diabetes therapy. GLP-1 stimulated insulin secretion in a glucose-dependent manner and is secreted by intestinal L cells. It also regulates blood glucose concentration, stomach motility, appetite, and body weight. These actions are mediated through G-protein-coupled receptors highly expressed on pancreatic beta cells and also exert indirect metabolic actions. Activation of GLP-1 receptors also produces nonglycemic effects in various tissues. The pleiotropic effects of GLP-1 have been recently reported. The mechanisms identified in preclinical studies have potential translational relevance for the treatment of disease. Here, the nonglycemic effects of GLP-1, especially those on the liver, central nervous system, and bone, were reviewed.
Appetite ; Blood Glucose ; Body Weight ; Central Nervous System ; Enteroendocrine Cells ; Glucagon ; Glucagon-Like Peptide 1 ; Incretins ; Insulin ; Insulin-Secreting Cells ; Liver ; Receptors, G-Protein-Coupled ; Stomach

One of the new promising therapies in treatment of diabetes mellitus is mesenchymal stem cells (MSCs) which have an interesting therapeutic potentiality based on their paracrine effect and transdifferentiation potentiality. Also obestatin improves the generation of functional β cells/islet-like cell clusters in vitro, suggesting implications for cell-based replacement therapy in diabetes. So the aim of this study was to evaluate the effect of combination of both MSCs and obestatin on an experimental model of type II diabetes mellitus (T2DM). Sixty male rats were divided into; group I (control group), group II (T2DM group) induced by administration of high fat diet (HFD) and injection of streptozotocin (STZ) in low dose, group III (T2DM treated with MSCs), group IV (T2DM treated with obestatin), group V (T2DM treated with MSCs and obestatin). Fasting blood glucose, C-peptide, insulin and lipid profile were measured. HOMA-IR and HOMA-β were calculated. Pancreatic expression of insulin, glucagon like peptide -1 (GLP-1) and pancreatic duodenal homeobox 1 (Pdx1) mRNA levels were measured. In addition pancreatic histological changes, insulin and Bax were analyzed by immunohistochemical examination of islets of Langerhans. Diabetic rats showed significant increase in HOMA-IR, serum glucose and lipid profile levels with significant decrease in insulin, HOMA-β, GLP-1 and Pdx1 levels. MSCs and obestatin caused significant improvement in all parameters with more significant improvement in combined therapy. The protective effects afforded by MSCs and obestatin may derive from improvement of the metabolic profile, antiapoptosis and by increase in pancreatic GLP-1and Pdx1 gene expression.
Animals ; Blood Glucose ; Bone Marrow* ; C-Peptide ; Diabetes Mellitus ; Diet, High-Fat ; Fasting ; Gene Expression ; Genes, Homeobox ; Ghrelin* ; Glucagon ; Glucagon-Like Peptide 1 ; Humans ; In Vitro Techniques ; Insulin ; Islets of Langerhans ; Male ; Mesenchymal Stromal Cells* ; Metabolome ; Models, Theoretical ; Rats* ; RNA, Messenger ; Streptozocin

AIM: To identify the glucose lowering ability and chronic treatment effects of a novel coumarin-glucagon-like peptide-1 (GLP-1) conjugate HJ07. METHOD: A receptor activation experiment was performed in HEK 293 cells and the glucose lowering ability was evaluated with hypoglycemic duration and glucose stabilizing tests. Chronic treatment was performed by daily injection of exendin-4, saline, and HJ07. Body weight and HbA1c were measured every week, and an intraperitoneal glucose tolerance test was performed before treatment and after treatment. RESULTS: HJ07 showed well-preserved receptor activation efficacy. The hypoglycemic duration test showed that HJ07 possessed a long-acting, glucose-lowering effect and the glucose stabilizing test showed that the antihyperglycemic activity of HJ07 was still evident at a predetermined time (12 h) prior to the glucose challenge (0 h). The long time glucose-lowering effect of HJ07 was better than native GLP-1 and exendin-4. Furthermore, once daily injection of HJ07 to db/db mice achieved long-term beneficial effects on HbA1c lowering and glucose tolerance. CONCLUSION The biological activity results of HJ07 suggest that HJ07 is a potential long-acting agent for the treatment of type 2 diabetes.
Animals ; Blood Glucose ; metabolism ; Coumarins ; pharmacology ; Diabetes Mellitus ; blood ; drug therapy ; Diabetes Mellitus, Type 2 ; drug therapy ; Exenatide ; Glucagon-Like Peptide 1 ; analogs & derivatives ; pharmacology ; therapeutic use ; Glucagon-Like Peptide-1 Receptor ; Glucose Tolerance Test ; Glycated Hemoglobin A ; metabolism ; HEK293 Cells ; Humans ; Hypoglycemic Agents ; pharmacology ; therapeutic use ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; Peptides ; pharmacology ; Receptors, Glucagon ; metabolism ; Venoms ; pharmacology

G-protein coupled receptor 119 (GPR119) has emerged as a novel target for the treatment of type 2 diabetes mellitus. GPR119 is involved in glucose-stimulated insulin secretion (GSIS) from the pancreatic beta-cells and intestinal cells. In this study, we identified a novel small-molecule GPR119 agonist, HD047703, which raises intracellular cAMP concentrations in pancreatic beta-cells and can be expected to potentiate glucose-stimulated insulin secretion from human GPR119 receptor stably expressing cells (CHO cells). We evaluated the acute efficacy of HD047703 by the oral glucose tolerance test (OGTT) in normal C57BL/6J mice. Then, chronic administrations of HD047703 were performed to determine its efficacy in various diabetic rodent models. Single administration of HD047703 caused improved glycemic control during OGTT in a dose-dependent manner in normal mice, and the plasma GLP-1 level was also increased. With respect to chronic efficacy, we observed a decline in blood glucose levels in db/db, ob/ob and DIO mice. These results suggest that HD047703 may be a potentially promising anti-diabetic agent.
Animals ; Blood Glucose ; Diabetes Mellitus, Type 2 ; Glucagon-Like Peptide 1 ; Glucose Tolerance Test ; GTP-Binding Proteins ; Humans ; Insulin ; Mice ; Plasma ; Rodentia