The effect of acute dual SGLT1/SGLT2 inhibition on incretin release and glucose metabolism after gastric bypass surgery.

The effect of acute dual SGLT1/SGLT2 inhibition on incretin release and glucose metabolism after gastric bypass surgery. Am J Physiol Endocrinol Metab. 2020 Mar 17;: Authors: Martinussen C, Veedfald S, Dirksen C, Bojsen-Møller KN, Svane MS, Wewer Albrechtsen NJ, van Hall G, Kristiansen VB, Fenger M, Holst JJ, Madsbad S Abstract Enhanced meal-related enteroendocrine secretion, particularly of glucagon-like peptide-1 (GLP-1), contributes to weight-loss and improved glycemia after Roux-en-Y gastric bypass (RYGB). Dietary glucose drives GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) secretion postoperatively. Understanding how glucose triggers incretin secretion following RYGB could lead to new treatments of diabetes and obesity. In vitro, incretin release depends on glucose absorption via sodium-glucose cotransporter-1 (SGLT1). We investigated the importance of SGLT1/SGLT2 for enteropancreatic hormone concentrations and glucose metabolism after RYGB in a randomized, controlled, crossover study. Ten RYGB-operated patients ingested 50 g of oral glucose ± acute pretreatment with 600 mg of the SGLT1/SGLT2-inhibitor canagliflozin. Paracetamol and 3-O-methyl-D-glucopyranose (3-OMG) were added to the glucose drink to evaluate rates of intestinal entry and absorption of glucose, respectively. Blood samples were collected for 4 h. The primary outcome was 4-h plasma GLP-1 (incremental area-under-the-curve, iAUC). Secondary outcomes include...
Source: Am J Physiol Endocri... - Category: Endocrinology Authors: Tags: Am J Physiol Endocrinol Metab Source Type: research

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Non-alcoholic fatty liver disease is the most common cause of liver disease in the United States, and is estimated to affect up to a quarter of adults in the world. It is defined by excess fat accumulating in the liver and usually occurs in people with obesity, high blood sugars (diabetes), abnormal cholesterol or triglyceride levels, or high blood pressure. These disorders often run together and as a group are called metabolic syndrome. The “non-alcoholic” part of “non-alcoholic fatty liver disease” is important to distinguish it from alcohol-related liver disease, which can also cause excess liver...
Source: Harvard Health Blog - Category: Consumer Health News Authors: Tags: Diet and Weight Loss Digestive Disorders Source Type: blogs
ConclusionsThere were rapid changes within 4 weeks after RYGB: signs of enhanced parasympathetic nerve activity, reduced morning cortisol, and enhanced incretin and glucagon responses to glucose. The findings suggest that neurohormonal mechanisms can contribute to the rapid improvement of insulin resistance and glycemia following RYGB in type 2 diabetes.
Source: Endocrine - Category: Endocrinology Source Type: research
From the Incretin Concept and the Discovery of GLP-1 to Today's Diabetes Therapy Jens Juul Holst* Department of Biomedical Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark Researchers have been looking for insulin-stimulating factors for more than 100 years, and in the 1960ties it was definitively proven that the gastrointestinal tract releases important insulinotropic factors upon oral glucose intake, so-called incretin hormones. The first significant factor identified was the duodenal glucose-dependent insulinotropic polypeptide, GIP, wh...
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research
Alyce M. Martin1, Emily W. Sun1, Geraint B. Rogers2,3 and Damien J. Keating1,4* 1Molecular and Cellular Physiology Laboratory, College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia 2Microbiome Research Laboratory, Flinders University, Adelaide, SA, Australia 3Infection and Immunity, South Australian Health and Medical Research Institute, Adelaide, SA, Australia 4Nutrition and Metabolism, South Australian Health and Medical Research Institute, Adelaide, SA, Australia The microbial community of the gut conveys significant benefits to host physiology. A clear relationship has now bee...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Conclusions: Bariatric surgery appears to be capable of partially reversing the obesity-related epigenome. The identification of potential epigenetic biomarkers predictive for the success of bariatric surgery may open new doors to personalized therapy for severe obesity. Introduction Obesity is currently a huge healthcare problem, worldwide, and is a risk factor for several diseases such as type 2 diabetes (T2D), cardiovascular disease and cancer (1). As the prevalence of obesity reaches pandemic proportions, this metabolic disease is estimated to become the biggest cause of mortality in the near future (2). In fact,...
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research
Conclusions: The overall CAN diagnosis was not associated with liraglutide-induced weight loss in overweight patients with type 1 diabetes. Assessed separately, better outcomes for several CAN measures were associated with higher weight loss, indicating that autonomic involvement in liraglutide-induced weight loss may exist. Introduction Glucagon-like peptide-1 (GLP-1) is a gut-derived hormone with anorexigenic properties (1). The GLP-1 receptor agonist (GLP-1RA) liraglutide is known to induce weight loss in patients with type 2 diabetes as well as in patients with type 1 diabetes (2–5). However, the exact me...
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research
CONCLUSIONS: RYGB perturbs multiple intestinal pathways, leading to decreased intestinal glucose absorption and increased incretin levels in both healthy and diabetic animals. In diabetic rats, intestinal glucose balance shifts towards glucose release. The portal vein as the gut-liver axis may integrate these intestinal changes to contribute to rapid changes in hepatic glucose and hormone handling. This fresh insight into the surgical physiology of RYGB raises the hope of less invasive alternatives. PMID: 30896970 [PubMed - as supplied by publisher]
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - Category: Physiology Authors: Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research
Bariatric surgery is currently the best treatment for type 2 diabetes mellitus (DM2) in patients with obesity. Although different surgical techniques produce different results, better glycemic control is achieved with surgical procedures compared to clinical treatments [1 –3].
Source: Surgery for Obesity and Related Diseases - Category: Surgery Authors: Tags: Original articles Source Type: research
Background: Type 2 diabetes mellitus is a disease correlated with obesity. Obese patients has suppressed incretin effect and inbalance of glycemic homeostasis. Studies have shown improvement in DM2 after Roux-en-Y gastric bypass (RYGB). The mechanisms of glycemic control may be long-term and short-term. The mechanisms of early action are linked to caloric restriction, improvement of insulin resistance, pancreatic beta cell function and return of the incretin effect through the increase of GLP1 and GIP, but data are conflicting.
Source: Surgery for Obesity and Related Diseases - Category: Surgery Authors: Source Type: research
ConclusionsRYGB is superior to SG in improving postprandial glycaemia and lipaemia and cholesterol profile 6  months postoperatively in non-diabetic, severely obese patients. These findings imply procedure-specific effects, such as the malabsorptive nature of RYGB, and less likely a different incretin postoperative response.
Source: Obesity Surgery - Category: Surgery Source Type: research
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