Track topics on Twitter Track topics that are important to you
Glucagon release from the pancreatic alpha-cells is regulated by glucose, but the underlying mechanisms are far from understood. It is known that the alpha-cell population is very heterogeneous, but - compared to the insulin-secreting beta-cells - the consequences of this cell-to-cell variation are much less studied. Since the alpha-cells are not electrically coupled, large differences in the single cell responses are to be expected, and this variation may contribute to the confusion regarding the mechanisms of glucose-induced suppression of glucagon release. Using mathematical modeling of alpha-cells with realistic cell-to-cell parameter variation based on recent experimental results, we show that the simulated alpha-cells exhibit great diversity in their electrophysiological behavior. To robustly reproduce experimental recordings from alpha-cell exposed to a rise in glucose levels, we must assume that both intrinsic mechanisms and paracrine signals contribute to glucose-induced changes in electrical activity. Our simulations suggest that the sum of different electrophysiological responses due to alpha-cell heterogeneity is involved in glucose-suppressed glucagon secretion, and that more than one mechanism contribute to control the alpha-cell populations' behavior. Finally, we apply regression analysis to our synthetic alpha-cell population to infer which membrane currents influence electrical activity in alpha-cells at different glucose levels. The results from such statistical modeling suggest possible disturbances underlying defect regulation of alpha-cell electrical behavior in diabetics. Thus, although alpha-cells appear to be inherently complex and heterogeneous as reflected in published data, realistic modeling of the alpha-cells at the population level provides insight into the mechanisms of glucagon release.
This article was published in the following journal.
Name: Journal of theoretical biology
The brain-type glycogen phosphorylase (pygb) is one of the rate-limiting enzyme in glycogenolysis that plays a crucial role in the pathogenesis of type 2 diabetes mellitus. Here we investigated the ro...
The molecular mechanisms of β-cell compensation to metabolic stress are poorly understood. We previously observed that nutrient-induced β-cell proliferation in rats is dependent on Epidermal Growth ...
Pancreatic β-cells express multiple phosphodiesterase (PDE) subtypes, but the specific roles for each in β-cell function, particularly in humans, is not clear. We evaluated the cellular role of PDE1...
Enzyme-resistant long-acting forms of the gut-derived peptide hormones, glucose-dependent insulinotropic polypeptide (GIP), xenin and oxyntomodulin (Oxm) have been generated, and exert beneficial effe...
Secretion of glucagon from the pancreatic alpha cells is conventionally seen as the first and most important defense against hypoglycemia. Recent findings, however, show that alpha cell signals stimul...
Glucagon-like peptide 1 is known to improve sensitivity of the pancreatic beta-cell. Further it inhibit secretion from the pancreatic alpha-cell by mechanisms not fully understand. With th...
Investigation of GLP-1 signalling in the glucose-lowering effect of increased carbohydrate content in the distal small intestines induced by alpha-glucosidase inhibition during meal ingest...
Inhibition of SGLT2 by specific inhibitors has been shown to reduce the renal threshold for glucose excretion in patients with type 2 diabetes mellitus (T2DM) and control subjects leading ...
The purpose of the current study is to determine if pre-exposure through video modeling will enhance testing compliance in a population of children who are receiving a diagnostic evaluatio...
The purpose of this study is to demonstrate the efficacy of alpha tocopherol for prevention contrast-induced nephropathy in CKD patients undergoing elective coronary procedures.
A fungal metabolite that blocks cytoplasmic cleavage by blocking formation of contractile microfilament structures resulting in multinucleated cell formation, reversible inhibition of cell movement, and the induction of cellular extrusion. Additional reported effects include the inhibition of actin polymerization, DNA synthesis, sperm motility, glucose transport, thyroid secretion, and growth hormone release.
An enzyme that catalyzes the hydrolysis of terminal 1,4-linked alpha-D-glucose residues successively from non-reducing ends of polysaccharide chains with the release of beta-glucose. It is also able to hydrolyze 1,6-alpha-glucosidic bonds when the next bond in sequence is 1,4.
1,4-alpha-D-Glucan-1,4-alpha-D-glucan 4-alpha-D-glucosyltransferase/dextrin 6 alpha-D-glucanohydrolase. An enzyme system having both 4-alpha-glucanotransferase (EC 126.96.36.199) and amylo-1,6-glucosidase (EC 188.8.131.52) activities. As a transferase it transfers a segment of a 1,4-alpha-D-glucan to a new 4-position in an acceptor, which may be glucose or another 1,4-alpha-D-glucan. As a glucosidase it catalyzes the endohydrolysis of 1,6-alpha-D-glucoside linkages at points of branching in chains of 1,4-linked alpha-D-glucose residues. Amylo-1,6-glucosidase activity is deficient in glycogen storage disease type III.
An enzyme that catalyzes the conversion of alpha D-glucose 1-phosphate to alpha D-glucose 6-phosphate. EC 184.108.40.206.
Enzymes that catalyze the exohydrolysis of 1,4-alpha-glucosidic linkages with release of alpha-glucose. Deficiency of alpha-1,4-glucosidase may cause GLYCOGEN STORAGE DISEASE TYPE II.
Pancreatitis Acute pancreatitis is inflammation of the pancreas caused by the release of activated pancreatic enzymes. Common triggers are biliary tract disease and chronic heavy alcohol intake. Diagnosis is based on clinical presentation...