Differential effects of imeglimin and metformin on insulin and incretin secretion-An exploratory randomized controlled trial.

Aims: Imeglimin is a new oral anti-diabetic drug with a similar structure to that of metformin; however, unlike metformin, clinical trials indicate that imeglimin elicits its glucose-lowering effect mainly by enhancement of insulin secretion. The comparative effects of the two drugs on incretin secretion remains to be elucidated.

Materials And Methods: A single-center, open-label, randomized controlled trial was conducted in patients with type 2 diabetes who were drug-naïve or were on a single oral hypoglycaemic agent (OHA).

Glucagon Stimulation Test and Insulin Secretory Capacity in the Clinical Assessment of Incretin-Based Therapy for Diabetes.

Evaluation of insulin secretory capacity is essential to understand the pathophysiologic condition of individuals with diabetes and assess the efficacy of drugs used in the treatment of this disease. The 1-mg i.v.

Effects of glucagon-like peptide-1 receptor agonists on secretions of insulin and glucagon and gastric emptying in Japanese individuals with type 2 diabetes: A prospective, observational study.

Aims/introduction: Differences in the glucose-lowering mechanisms of glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been noted. Clarifying these differences could facilitate the choice of optimal drugs for individuals with type 2 diabetes and requires investigation in a clinical setting.

Materials And Methods: A single-arm, prospective, observational study was conducted to evaluate the effects of various GLP-1RAs on postprandial glucose excursion, secretions of insulin and glucagon as well as on the gastric emptying rate.

Carbonic anhydrase 8 (CAR8) negatively regulates GLP-1 secretion from enteroendocrine cells in response to long-chain fatty acids.

Glucagon-like peptide-1 (GLP-1) is an incretin secreted from enteroendocrine preproglucagon (PPG)-expressing cells (traditionally known as L cells) in response to luminal nutrients that potentiates insulin secretion. Augmentation of endogenous GLP-1 secretion might well represent a novel therapeutic target for diabetes treatment in addition to the incretin-associated drugs currently in use. In this study, we found that PPG cells substantially express carbonic anhydrase 8 (CAR8), which has been reported to inhibit inositol 1,4,5-trisphosphate (IP3) binding to the IP3 receptor and subsequent Ca efflux from the endoplasmic reticulum in neuronal cells.

Single-Cell Transcriptome Analysis Dissects the Replicating Process of Pancreatic Beta Cells in Partial Pancreatectomy Model.

Heterogeneity of gene expression and rarity of replication hamper molecular analysis of β-cell mass restoration in adult pancreas. Here, we show transcriptional dynamics in β-cell replication process by single-cell RNA sequencing of murine pancreas with or without partial pancreatectomy. We observed heterogeneity of -expressing β-cells and identified the one cluster as replicating β-cells with high expression of cell proliferation markers and .

Acromegaly accompanied by diabetes mellitus and polycystic kidney disease.

Acromegaly is characterized by autonomous excessive growth hormone (GH) secretion, generally due to GH-producing pituitary adenoma, and is associated with various systemic comorbidities including diabetes mellitus. Polycystic kidney disease (PKD) is characterized by the growth of numerous cysts in the kidneys that deteriorate renal function. While possible renal effects of excessive GH exposure have been a current issue in experimental medicine, only five cases of coexisting acromegaly and PKD have been reported previously, and little is known regarding the influence of acromegaly on renal disease.

Generation and Characterization of a Novel Mouse Model That Allows Spatiotemporal Quantification of Pancreatic β-Cell Proliferation.

Pancreatic β-cell proliferation has been gaining much attention as a therapeutic target for the prevention and treatment of diabetes. In order to evaluate potential β-cell mitogens, accurate and reliable methods for the detection and quantification of the β-cell proliferation rate are indispensable. In this study, we developed a novel tool that specifically labels replicating β-cells as mVenus cells by using RIP-Cre; R26Fucci2aR mice expressing the fluorescent ubiquitination-based cell cycle indicator Fucci2a in β-cells.

GPR40 activation initiates store-operated Ca entry and potentiates insulin secretion via the IP3R1/STIM1/Orai1 pathway in pancreatic β-cells.

The long-chain fatty acid receptor GPR40 plays an important role in potentiation of glucose-induced insulin secretion (GIIS) from pancreatic β-cells. Previous studies demonstrated that GPR40 activation enhances Ca release from the endoplasmic reticulum (ER) by activating inositol 1,4,5-triphosphate (IP3) receptors. However, it remains unknown how ER Ca release via the IP3 receptor is linked to GIIS potentiation.

Twincretin as a potential therapeutic for the management of type 2 diabetes with obesity.

Unimolecular peptide-based dual agonists against glucagon-like peptide-1 receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR) have been gaining much attention recently as novel antidiabetic agents that can potentially control glycemia and bodyweight. Although GLP-1 and GIP both enhance insulin secretion and subsequently ameliorate postprandial glucose excursion, most research has focused on GLP-1R as a therapeutic target for type 2 diabetes. This is partly because the effects of GIPR activation on glycemia and bodyweight have been controversial.

Reply to the comment of Wilbrink et al. on Retrospective analysis of liraglutide and basal insulin combination therapy in Japanese type 2 diabetes: The association between remaining β-cell function and the achievement of the HbA1c target 1 year after initiation.

We have reported that the HbA1c-lowering effects of liraglutide/basal insulin combination rely on remaining β-cell function and that the cut-off value of the C-peptide immunoreactivity index (CPI), a β-cell function-related index frequently used in Japanese clinical settings, is 1.103 for the achievement of HbA1c <7.0% at 54 weeks after initiating the liraglutide/basal insulin combination.

Relationship between deterioration of glycated hemoglobin-lowering effects in dipeptidyl peptidase-4 inhibitor monotherapy and dietary habits: Retrospective analysis of Japanese individuals with type 2 diabetes.

The present study was designed to assess possible relationships between deterioration of the glycated hemoglobin (HbA1c)-lowering effects in dipeptidyl peptidase-4 inhibitor (DPP4i) monotherapy and macronutrient intake among individuals with type 2 diabetes. Type 2 diabetes patients who began and continued DPP4i monotherapy without any prescription change for 1 year were retrospectively stratified into two groups: (i) patients who maintained their HbA1c levels during the 0.5- to 1-year period after DPP4i initiation (group A, ΔHbA1c [1-0.

Retrospective analysis of liraglutide and basal insulin combination therapy in Japanese type 2 diabetes patients: The association between remaining β-cell function and the achievement of the glycated hemoglobin target 1 year after initiation.

Aims/introduction: The glucose-lowering effects of the glucagon-like peptide-1 receptor agonist, liraglutide, have been shown to rely on remaining β-cell function. However, the possible associations of remaining β-cell function with the glucose-lowering effects of liraglutide in combination with basal insulin remain unknown and warrant investigation.

Materials And Methods: This was a single-center, retrospective, observational study carried out in a private hospital in Osaka, Japan.

Oral Administration of Apple Procyanidins Ameliorates Insulin Resistance via Suppression of Pro-Inflammatory Cytokine Expression in Liver of Diabetic ob/ob Mice.

Procyanidins, the main ingredient of apple polyphenols, are known to possess antioxidative and anti-inflammatory effects associated closely with the pathophysiology of insulin resistance and type 2 diabetes. We investigated the effects of orally administered apple procyanidins (APCs) on glucose metabolism using diabetic ob/ob mice. We found no difference in body weight or body composition between mice treated with APCs and untreated mice.

Src regulates insulin secretion and glucose metabolism by influencing subcellular localization of glucokinase in pancreatic β-cells.

Aims/introduction: Src, a non-receptor tyrosine kinase, regulates a wide range of cellular functions, and hyperactivity of Src is involved in impaired glucose metabolism in pancreatic β-cells. However, the physiological role of Src in glucose metabolism in normal, unstressed β-cells remains unclear. In the present study, we investigated the role of Src in insulin secretion and glucose metabolism.

Retrospective analysis of safety and efficacy of liraglutide monotherapy and sulfonylurea-combination therapy in Japanese type 2 diabetes: Association of remaining β-cell function and achievement of HbA1c target one year after initiation.

Aims: The GLP-1 receptor agonist liraglutide improves impaired pancreatic β-cell function, thereby exerting glucose-lowering effects. However, the association of remaining β-cell function with long-term therapeutic efficacy of liraglutide remains largely unknown.

Methods: Patients with type 2 diabetes who started liraglutide as monotherapy or sulfonylurea-combination therapy were retrospectively analyzed to identify possible associations of indices related to β-cell function including increments of C-peptide immunoreactivity in glucagon stimulation test (GST-ΔCPR) with achievement of HbA1c <7.

Glucagon-like peptide-1 receptor agonist therapeutics for total diabetes management: assessment of composite end-points.

Assessment of the benefits of anti-diabetic drugs for type 2 diabetes requires analysis of composite end-points, taking HbA1c, bodyweight, hypoglycemia and other metabolic parameters into consideration; continuous, optimal glycemic control as well as bodyweight, blood pressure and lipid levels are critical to prevent micro- and macro-vascular complications. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are now established as an important total treatment strategy for type 2 diabetes, exerting glucose-lowering effects with little hypoglycemia risk and also ameliorating bodyweight, blood pressure and lipid levels, which are therapeutic targets for prevention of complications of the disease. The available data strongly suggest only beneficial effects of GLP-1RAs; however, long-term evaluation of the relevant composite end-points including health-related quality of life and cost-effectiveness remain to be investigated in adequately powered, prospective, controlled clinical trials.

Enhanced glucagon-like peptide-1 secretion in a patient with glucagonoma: implications for glucagon-like peptide-1 secretion from pancreatic α cells in vivo.

We examined GLP-1 secretion from the pancreas of a patient with glucagonoma and pancreatic resection by measuring GLP-1 after meal ingestion or selective arterial calcium injection, and immunohistochemical analysis. Our findings support the notion that GLP-1 is secreted from pancreatic α cells in humans.