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Regulation of Blood Glucose
Published in Robert B. Northrop, Endogenous and Exogenous Regulation and Control of Physiological Systems, 2020
The hormones insulin and glucagon are proteins manufactured in the pancreas, insulin by the beta cells and glucagon by the alpha cells. Insulin consists of two sulfur-linked amino acid chains with a total of 51 amino acids, and it has a molecular weight of 5808. Glucagon is a single chain of 29 amino acids, with a molecular weight of 3485. The molecular structures of both insulin and glucagon are known exactly.59 Both hormones are secreted into the hepatic portal venous system via the pancreaticoduodenal vein. Thus liver cells are the first to receive the secreted insulin and glucagon and generally see higher concentrations of these hormones than are present in the systemic plasma.
Bio-medical potential of chalcone derivatives and their metal complexes as antidiabetic agents: a review
Published in Journal of Coordination Chemistry, 2021
The α-glucosidase converts dietary starch and complex carbohydrates (oligosaccharides and polysaccharides) into simple sugars viz. glucose by breaching the glycosidic bonds present in them and also delays carbohydrate digestion/absorption [45]. Alpha cells of the small intestine, especially α-glucosidase which is present predominantly in the proximal half [46], produces glucagon which upon gluconeogenesis produces glucose followed by its release to the bloodstream [47]. This increase of excess glucose in the bloodstream causes hyperglycemia and this leads to development of T2DM because of lack of response of adipose tissues to insulin. In detailed mechanism, excessive glutamate consumption with food disturbs the glutamate homeostatis and elevated glutamate concentrations activate the α-cells via AMPA/kinate receptors and stimulates glucagon secretion [48, 49]. Glucagon secreted by the pancreatic alpha cells of the pancreatic islets is the body’s principal hyperglycemic hormone. Glucagon secretion is also under paracrine control by insulin and follows the ‘switch-off’ hypothesis, which means hyper secretion of glucagon when insulin secretion is low [50]. This whole mechanism is shown in Figure 3 in the form of a cycle.
Adaptive controller based an extended model of glucose-insulin-glucagon system for type 1 diabetes
Published in International Journal of Modelling and Simulation, 2023
Mahour Saoussane, Tadjine Mohammed, Chakir Mesaoud
Insulin and glucagon are pancreatic hormones, secreted from pancreatic beta and alpha cells, respectively [1]. Diabetes mellitus is a metabolic disease characterized by an inadequate production of insulin, or a deficient sensitivity to insulin. Diabetes is classified into: ‘type1 diabetes’ and ‘type 2 diabetes’. In type 1 diabetes (T1DM), the immune system attacks the b-cells in the pancreas, which produce insulin [2]. The treatment of T1D currently consists of multiple daily injections or continuous subcutaneous delivery of insulin through a pump.
Closed-loop control in insulin pumps for type-1 diabetes mellitus: safety and efficacy
Published in Expert Review of Medical Devices, 2020
One way to address the challenges around delayed insulin action as well as the hypoglycemia risk associated with tighter glycemic targets is to use adjunctive hormone therapy. In healthy individuals, pancreatic alpha cells secret glucagon in response to falling glucose levels to maintain normoglycaemia. This response is lost in people with type 1 diabetes, so even when insulin delivery is suspended, hypoglycemia may occur. Dual hormone closed-loop systems aim to emulate this physiological process more closely by directing the delivery of both insulin and glucagon with the latter being delivered when hypoglycemia occurs or is predicted. There are several barriers to dual-hormone systems including the need for a second or dual-chamber infusion pump and a lack of stable formulations of glucagon [81]. Studies applying these systems have all been of limited size and duration. Although more recent results show an increased time in range for dual-hormone systems compared to insulin-only therapy [82,83 and 84], long-term safety and efficacy data are not yet available. Glucagon is associated with increased gastrointestinal side-effects and long-term effects of regular subcutaneous glucagon administration on hepatic and cardiovascular systems are yet to be assessed [19,81]. Another approach that has been trialed in dual-hormone systems is pramlintide. It is a synthetic analogue of amylin, a pancreatic protein that slows gastric emptying and is largely absent in people with type 1 diabetes. Pramlintide has been shown to reduce postprandial spikes in blood glucose more effectively than insulin alone [19]. A recent inpatient study by Haidar et al. showed an increased time in range when using a rapid insulin-and-pramlintide artificial pancreas compared to a rapid insulin-only artificial pancreas (84% compared to 74% time in range, p = 0.0014), which was mainly due to a daytime increase in time in range on the dual-hormone system [85]. Similar to glucagon, pramlintide requires a separate infusion pump, although co-formulations with insulin are in development. Other limitations are its dosage cap and potential side-effects such as nausea and increased risk of hypoglycemia with pre-meal administration [86].