Glucagon

Obesity is a significant risk factor for health issues like type 2 diabetes and cardiovascular disease. It often proves resistant to traditional lifestyle interventions, prompting a need for more precise therapeutic strategies. This has led to a focus on signaling pathways and neuroendocrine mechanisms to develop targeted obesity treatments. Recent developments in obesity management have been revolutionized by introducing novel glucagon-like peptide-1 (GLP-1) based drugs, such as semaglutide and tirzepatide...

Diabetes mellitus is a significant risk factor for both ischaemic and haemorrhagic stroke, affecting up to a third of individuals with cerebrovascular diseases. Beyond being a risk factor for stroke, diabetes and hyperglycaemia have a negative impact on outcomes after ischaemic and haemorrhagic stroke. Hyperglycaemia during the acute ischaemic stroke phase is associated with a higher risk of haemorrhagic transformation and poor functional outcome, with evidence in favour of early intervention to limit and manage severe hyperglycaemia...

Autoimmune liver diseases are associated with an increased risk of diabetes, yet the underlying mechanisms remain unknown. In this cross-sectional study, we investigated the glucose-regulatory disturbances in patients with autoimmune hepatitis (AIH, n=19), primary biliary cholangitis (PBC, n=15), and primary sclerosing cholangitis (PSC, n=6). Healthy individuals (n=24) and patients with metabolic dysfunction-associated steatotic liver disease (MASLD, n=18) were included as controls. Blood samples were collected during a 120 min oral glucose tolerance test...

Diabetes is a metabolic disorder whose prevalence has become a worrying condition in recent decades. Chronic diabetes can result in serious health conditions such as impaired kidney function, stroke, blindness, and myocardial infarction. Despite a variety of currently available treatments, cases of diabetes and its complications are on the rise. This review article provides a comprehensive account of the ameliorative effect of prebiotics and probiotics individually or in combination i.e. synbiotics on health complications induced by Type 2 Diabetes Mellitus (T2DM)...

BACKGROUND: The introduction of injectable glucagon-like peptide-1 (GLP-1) receptor agonists like Ozempic and Wegovy has transformed weight loss in plastic surgery patients, often leading to excess skin and soft tissue amendable to body contouring procedures. OBJECTIVES: This project aims to examine the relationship between injectable GLP-1 receptor agonist use and the growing need for body contouring surgeries, focusing on trunk and extremity procedures. METHODS: A retrospective analysis was conducted using the PearlDiver database, examining prescription data for Ozempic, Wegovy, and liraglutide, and correlating these with body contouring procedures across 30 U...

AIM: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve glycaemic control and cardio-renal outcomes for people with type 2 diabetes (T2D). However, geographic and socio-economic variation in use is not well understood. METHODS: We identified 367 829 New South Wales residents aged ≥40 years who dispensed metformin in 2020 as a proxy for T2D. We estimated the prevalence of use of other glucose-lowering medicines among people with T2D and the prevalence of SGLT2i and GLP-1RA use among people using concomitant T2D therapy (i...

AIM: To assess the use of non-insulin antidiabetic medicines in China. MATERIALS AND METHODS: We analysed the national procurement data for 29 non-insulin antidiabetic medicines from nine subgroups in China from 2015 to 2022. We estimated the number of defined daily doses (DDDs) procured per year in seven regions of China for nine subgroups and adjusted the data by the number of patients with diabetes. For each subgroup, the regional ratio was calculated by comparing the procurement per patient in each region with the procurement nationwide...

Type 2 diabetes mellitus (T2DM) is one of the world's principal metabolic diseases characterized by chronic hyperglycemia. The gut incretin hormones, glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP), which has been proposed as a new treatment for T2DM, are extensively metabolized by Dipeptidyl peptidase 4 (DPP-4). Inhibitors of DPP-4 block the degradation of GLP-1 and GIP and may increase their natural circulating levels, favoring glycemic control in T2DM. A novel and potent selective inhibitor of DPP-4 with an 8-purine derived structure ( 1 ) has been developed and tested in vitro and in vivo in Zücker obese diabetic fatty (ZDF) rats, an experimental model of the metabolic syndrome and T2DM to assess the inhibitory activity using vildagliptin as reference standard...

Metformin is the initial medication recommended for the treatment of type 2 diabetes mellitus (T2DM). In addition to diabetes treatment, the function of metformin also can be anti-aging, antiviral, and anti-inflammatory. Nevertheless, further exploration is required to fully understand its mode of operation. Historically, the liver has been acknowledged as the main location where metformin reduces glucose levels, however, there is increasing evidence suggesting that the gastrointestinal tract also plays a significant role in its action...

Coronary heart disease remains a major global health challenge, with a clear need for enhanced early risk assessment. This study aimed to elucidate metabolic signatures across various stages of coronary heart disease and develop an effective multiclass diagnostic model. Using metabolomic approaches, gas chromatography-mass and liquid chromatography-tandem mass spectrometry were used to analyze plasma samples from healthy controls, patients with stable angina pectoris, and those with acute myocardial infarction...

BACKGROUND AND AIMS: Randomized clinical trials have demonstrated the ability of glucagon-like peptide-1 analogues (GLP-1RAs) to reduce atherosclerotic cardiovascular disease events in patients with type 2 diabetes (T2D). How GLP-1RAs modulate diabetic atherosclerosis remains to be determined yet. METHODS: The OPTIMAL study was a prospective randomized controlled study to compare the efficacy of 48-week continuous glucose monitoring- and HbA1c-guided glycemic control on near infrared spectroscopty (NIRS)/intravascular ultrasound (IVUS)-derived plaque measures in 94 statin-treated patients with T2D (jRCT1052180152, UMIN000036721)...

Cardiac hypertrophy is the most prevalent compensatory heart disease that ultimately leads to spontaneous heart failure. Mounting evidence suggests that microRNAs (miRs) and endogenous hydrogen sulfide (H2 S) play a crucial role in the regulation of cardiac hypertrophy. In this study, we aimed to investigate whether inhibition of miR-27a could protect against cardiac hypertrophy by modulating H2 S signaling. We established a model of cardiac hypertrophy by obtaining hypertrophic tissue from mice subjected to transverse aortic constriction (TAC) and from cells treated with angiotensin-II...

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People with obesity and type 2 diabetes have a high prevalence of metabolic-associated steatotic liver disease, hyperlipidemia and cardiovascular disease. Glucagon increases hepatic glucose production; it also decreases hepatic fat accumulation, improves lipidemia and increases energy expenditure. Pharmaceutical strategies to antagonize the glucagon receptor improve glycemic outcomes in people with diabetes and obesity, but they increase hepatic steatosis and worsen dyslipidemia. Co-agonism of the glucagon and glucagon-like peptide-1 (GLP-1) receptors has emerged as a promising strategy to improve glycemia in people with diabetes and obesity...

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent chronic liver disease that can progress to end-stage conditions with life-threatening complications, but no pharmacologic therapy has been approved. Drug delivery systems such as lipid nanocapsules (LNC) are very versatile platforms that are easy to produce and can induce the secretion of the native glucagon-like peptide 1 (GLP-1) when orally administered. GLP-1 analogs are currently being studied in clinical trials in the context of MASLD...

Diabetes and obesity are closely interlinked. Obesity is a major risk factor for the development of type 2 diabetes mellitus and appears to be an important risk factor for diabetic micro- and macrovascular complications. Management of hyperglycaemia in people with diabetes is important to reduce diabetes-related complications. Previously, there was a significant tension between management of hyperglycaemia and mitigating weight gain. Older drugs, such as sulfonylureas, glitazones, and insulin, although effective antihyperglycaemic agents, tend to induce weight gain...

Obesity is a chronic disease associated with increased morbidity and mortality. Bariatric surgery can lead to sustained long-term weight loss (WL) and improvement in multiple obesity-related complications, but it is not scalable at the population level. Over the past few years, gut hormone-based pharmacotherapies for obesity and type 2 diabetes mellitus (T2DM) have rapidly evolved, and combinations of glucagon-like peptide 1 (GLP1) with other gut hormones (glucose-dependent insulinotropic polypeptide (GIP), glucagon, and amylin) as dual or triple agonists are under investigation to enhance and complement the effects of GLP1 on WL and obesity-related complications...

The glucagon receptor family are typical class B1 G protein-coupled receptors (GPCRs) with important roles in metabolism, including the control of pancreas, brain, and liver function. As proteins with 7 transmembrane domains, GPCRs are intimately in contact with lipid bilayers and therefore can be putatively regulated by interactions with their lipidic components, including cholesterol, sphingolipids, and other lipid species. Additionally, these receptors, as well as the agonists they bind to, can undergo lipid modifications, which can influence their binding capacity and/or elicit modified or biased signalling profiles...

Islets of Langerhans are anatomically dispersed within the pancreas and exhibit regulatory coordination between islets in response to nutritional and inflammatory stimuli. However, within individual islets, there is also multi-faceted coordination of function between individual beta-cells, and between beta-cells and other endocrine and vascular cell types. This is mediated partly through circulatory feedback of the major secreted hormones, insulin and glucagon, but also by autocrine and paracrine actions within the islet by a range of other secreted products, including somatostatin, urocortin 3, serotonin, glucagon-like peptide-1, acetylcholine, and ghrelin...

Diabetic kidney disease (DKD) is a chronic microvascular complication in patients with diabetes mellitus (DM) and the leading cause of end-stage kidney disease (ESKD). Although glomerulosclerosis, tubular injury and interstitial fibrosis are typical damages of DKD, the interplay of different processes (metabolic factors, oxidative stress, inflammatory pathway, fibrotic signaling, and hemodynamic mechanisms) appears to drive the onset and progression of DKD. A growing understanding of the pathogenetic mechanisms, and the development of new therapeutics, is opening the way for a new era of nephroprotection based on precision-medicine approaches...