Plasma Mir-193b-3p Is Elevated in Type 2 Diabetes and Could Impair Glucose Metabolism

Metformin is the first-line pharmacotherapy for treating type 2 diabetes mellitus (T2DM); however, its mechanism of modulating glucose metabolism is elusive. Recent advances have identified the gut as a potential target of metformin. As patients with metabolic disorders exhibit dysbiosis, the gut microbiome has garnered interest as a potential target for metabolic disease. Henceforth, studies have focused on unraveling the relationship of metabolic disorders with the human gut microbiome. According to various metagenome studies, gut dysbiosis is evident in T2DM patients. Besides this, alterations in the gut microbiome were also observed in the metformin-treated T2DM patients compared to the non-treated T2DM patients. Thus, several studies on rodents have suggested potential mechanisms interacting with the gut microbiome, including regulation of glucose metabolism, an increase in short-chain fatty acids, strengthening intestinal permeability against lipopolysaccharides, modulating the immune response, and interaction with bile acids. Furthermore, human studies have demonstrated evidence substantiating the hypotheses based on rodent studies. This review discusses the current knowledge of how metformin modulates T2DM with respect to the gut microbiome and discusses the prospect of harnessing this mechanism in treating T2DM.

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Potential of Creatine in Glucose Management and Diabetes

Nutrients ◽

10.3390/nu13020570 ◽

2021 ◽

Vol 13 (2) ◽

pp. 570

Author(s):

Marina Yazigi Solis ◽

Guilherme Giannini Artioli ◽

Bruno Gualano

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Glucose Metabolism ◽

Exercise Training ◽

Creatine Supplementation ◽

Small Scale ◽

Therapeutic Effects ◽

Glucose Management

Creatine is one of the most popular supplements worldwide, and it is frequently used by both athletic and non-athletic populations to improve power, strength, muscle mass and performance. A growing body of evidence has been identified potential therapeutic effects of creatine in a wide variety of clinical conditions, such as cancer, muscle dystrophy and neurodegenerative disorders. Evidence has suggested that creatine supplementation alone, and mainly in combination with exercise training, may improve glucose metabolism in health individuals and insulin-resistant individuals, such as in those with type 2 diabetes mellitus. Creatine itself may stimulate insulin secretion in vitro, improve muscle glycogen stores and ameliorate hyperglycemia in animals. In addition, exercise induces numerous metabolic benefits, including increases in insulin-independent muscle glucose uptake and insulin sensitivity. It has been speculated that creatine supplementation combined with exercise training could result in additional improvements in glucose metabolism when compared with each intervention separately. The possible mechanism underlying the effects of combined exercise and creatine supplementation is an enhanced glucose transport into muscle cell by type 4 glucose transporter (GLUT-4) translocation to sarcolemma. Although preliminary findings from small-scale trials involving patients with type 2 diabetes mellitus are promising, the efficacy of creatine for improving glycemic control is yet to be confirmed. In this review, we aim to explore the possible therapeutic role of creatine supplementation on glucose management and as a potential anti-diabetic intervention, summarizing the current knowledge and highlighting the research gaps.

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Activation of heat shock response improves glucose metabolism and inflammation in obese subjects with type 2 diabetes

Diabetes Research and Clinical Practice ◽

10.1016/s0168-8227(16)31049-x ◽

2016 ◽

Vol 120 ◽

pp. S61

Author(s):

Tatsuya Kondo ◽

Rieko Goto ◽

Kaoru Ono ◽

Sayaka Kitano ◽

Motoyuki Igata ◽

...

Keyword(s):

Type 2 Diabetes ◽

Heat Shock ◽

Glucose Metabolism ◽

Heat Shock Response ◽

Shock Response ◽

Obese Subjects

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Type 2 Diabetes Dysregulates Glucose Metabolism in Cardiac Progenitor Cells

Journal of Biological Chemistry ◽

10.1074/jbc.m116.722496 ◽

2016 ◽

Vol 291 (26) ◽

pp. 13634-13648 ◽

Cited By ~ 23

Author(s):

Joshua K. Salabei ◽

Pawel K. Lorkiewicz ◽

Parul Mehra ◽

Andrew A. Gibb ◽

Petra Haberzettl ◽

...

Keyword(s):

Type 2 Diabetes ◽

Glucose Metabolism ◽

Progenitor Cells ◽

Cardiac Progenitor Cells

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Effects of efpeglenatide versus liraglutide on gastric emptying, glucose metabolism and beta-cell function in people with type 2 diabetes: an exploratory, randomized phase Ib study

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2021-002208 ◽

2021 ◽

Vol 9 (1) ◽

pp. e002208

Author(s):

Marcus Hompesch ◽

Jahoon Kang ◽

OakPil Han ◽

Michael E Trautmann ◽

Christopher H Sorli ◽

...

Keyword(s):

Type 2 Diabetes ◽

Gastric Emptying ◽

Glucose Metabolism ◽

Beta Cell ◽

Beta Cell Function ◽

Cell Function ◽

Phase Ib ◽

Link Type ◽

Drug Concentrations

IntroductionTo evaluate the effects of efpeglenatide, a long-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA), on gastric emptying, glucose metabolism, and islet beta-cell function versus liraglutide and placebo in people with type 2 diabetes.Research design and methodsThis phase Ib study (ClinicalTrials.gov identifier: NCT02059564) randomized participants (n=47) to three cohorts. Within the first two cohorts, participants were randomized to placebo, efpeglenatide 6 mg weekly (QW; first cohort), or efpeglenatide 16 mg monthly (QM; second cohort). The third cohort received liraglutide 1.8 mg daily (QD). Gastric emptying was assessed through the pharmacokinetic (PK) profile of acetaminophen at baseline and steady state. Glucose metabolism and beta-cell function were assessed based on mixed-meal tolerance testing and a graded glucose infusion procedure.ResultsTreatment duration was approximately 3 months for efpeglenatide 16 mg QM and 1 month for efpeglenatide 6 mg QW and liraglutide. At peak drug concentrations, efpeglenatide 6 mg QW was non-inferior to liraglutide 1.8 mg QD in delaying gastric emptying, as assessed by acetaminophen PK (lower bound of 90% CI for the efpeglenatide:liraglutide ratio >0.8 for area under the curve (AUC)0–120, AUC0–180, AUC0–360 and maximum concentration (Cmax)). Efpeglenatide 16 mg QM did not decrease the rate of gastric emptying to as great an extent as liraglutide (ie, non-inferiority was not shown). Compared with liraglutide, both efpeglenatide dosing regimens demonstrated comparable or more favorable glucometabolic effects and improved beta-cell function. All gastrointestinal adverse events reported with efpeglenatide were mild or moderate in severity and transient over treatment and follow-up.ConclusionsThe glucometabolic effects of efpeglenatide 6 mg QW and 16 mg QM were comparable to liraglutide. Additional studies are necessary to further examine these benefits of efpeglenatide.Trial registration numberNCT02059564.

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116-LB: Efruxifermin Is Associated with Improved Glucose Metabolism in Patients with NASH and Type 2 Diabetes

Diabetes ◽

10.2337/db21-116-lb ◽

2021 ◽

Vol 70 (Supplement 1) ◽

pp. 116-LB

Author(s):

JUAN PABLO FRIAS ◽

RESHMA SHRINGARPURE ◽

ERIK J. TILLMAN ◽

CHEN HU ◽

ERICA FONG ◽

...

Keyword(s):

Type 2 Diabetes ◽

Glucose Metabolism

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MECHANISMS IN ENDOCRINOLOGY: FXR signalling: a novel target in metabolic diseases

Acta Endocrinologica ◽

10.1530/eje-20-1410 ◽

2021 ◽

Vol 184 (5) ◽

pp. R193-R205

Author(s):

David P Sonne

Keyword(s):

Type 2 Diabetes ◽

Bile Acid ◽

Gastrointestinal Tract ◽

Glucose Metabolism ◽

Metabolic Diseases ◽

Farnesoid X Receptor ◽

Optimal Size ◽

Lipid Digestion ◽

Alcoholic Fatty Liver

During the last decades, it has become clear that the gastrointestinal tract plays a pivotal role in the regulation of glucose homeostasis. More than 40 hormones originate from the gastrointestinal tract and several of these impact glucose metabolism and appetite regulation. An astonishing example of the gut’s integrative role in glucose metabolism originates from investigations into bile acid biology. From primary animal studies, it has become clear that bile acids should no longer be labelled as simple detergents necessary for lipid digestion and absorption but should also be recognised as metabolic regulators implicated in lipid, glucose and energy metabolism. The nuclear farnesoid X receptor (FXR) is a part of an exquisite bile acid-sensing system that among other things ensures the optimal size of the bile acid pool. In addition, intestinal and hepatic FXR also impact the regulation of several metabolic processes such as glucose and lipid metabolism. Accordingly, natural and synthetic FXR agonists and certain FXR-regulated factors (i.e. fibroblast growth factor 19 (FGF19)) are increasingly being evaluated as treatments for metabolic diseases such as type 2 diabetes and non-alcoholic fatty liver disease (and its inflammatory version, non-alcoholic steatohepatitis). Interestingly, decreased FXR activation also benefits glucose metabolism. This can be obtained by reducing bile acid absorption using bile acid sequestering agents (approved for the treatment of type 2 diabetes) or inhibitors of intestinal bile acid transporters,that is the apical sodium-dependent bile acid transporter (ASBT). This article discusses recent clinical trials that provide insights about the role of FXR-FGF19-targetted therapy for the treatment of metabolic diseases.

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