Abstract
Glucose metabolism is the initiator of a large number of molecular secretory processes in β cells. Cyclic nucleotides as a second messenger are the main physiological regulators of these processes and are functionally divided into compartments in pancreatic cells. Their intracellular concentration is limited by hydrolysis led by one or more phosphodiesterase (PDE) isoenzymes. Literature data confirmed multiple expressions of PDEs subtypes, but the specific roles of each in pancreatic β-cell function, particularly in humans, are still unclear. Isoforms present in the pancreas are also found in various tissues of the body. Normoglycemia and its strict control are supported by the appropriate release of insulin from the pancreas and the action of insulin in peripheral tissues, including processes related to homeostasis, the regulation of which is based on the PDE- cyclic AMP (cAMP) signaling pathway. The challenge in developing a therapeutic solution based on GSIS (glucose-stimulated insulin secretion) enhancers targeted at PDEs is the selective inhibition of their activity only within β cells. Undeniably, PDEs inhibitors have therapeutic potential, but some of them are burdened with certain adverse effects. Therefore, the chance to use knowledge in this field for diabetes treatment has been postulated for a long time.
Highlights
Glucose is the major physiological stimulator of insulin secretion from pancreatic β cells
Cyclic nucleotides are responsible for regulation of many essential to physiological and pathophysiological processes. cyclic AMP (cAMP) is involved in the regulation of energy metabolism, many processes depend on its presence and concentration, including the rate of triglyceride lipolysis, and cAMP signaling pathways modulate gluconeogenesis, glycogenolysis, and thermogenesis [8]
The role of cyclic guanosine monophosphate as a nucleotide modeling the process of insulin secretion and glucose metabolism has not yet been fully explained
Summary
Glucose is the major physiological stimulator of insulin secretion from pancreatic β cells. The first and second phases of insulin release are quantitatively dependent on the enhancement of the metabolic pathway by approximately 50% [1,2], and its increase in plasma leads to a significant rise in glucose uptake and metabolism in pancreatic β cells. The cascade signal results in plasma membrane depolarization, opening of voltage-gated plasmalemic Ca2+ channels (VGCC), and the influx of calcium ions [3,4]. The consequence of these occurrences is an increase in intracellular calcium concentration ([Ca2+]i) resulting from the inflow through plasmalemmal voltage-gated calcium channels. It was observed that exocytosis of insulin is stimulated by an increases in cAMP [6,7]
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