Polski
Glucocorticoids and beta-cell function
Abstract
Glucocorticoids (GCs) play a pivotal role in carbohydrate metabolism. They counteract insulin by decreasing peripheral glucose uptake and stimulating hepatic gluconeogenesis, although they are best known for inducing insulin resistance (IR). Moreover, GCs may attenuate the incretin effect. Nevertheless, their direct impact on beta cells is not fully defined. This review aims to present the current understanding of this subject.
Humans exposed to GC excess display IR, impaired glucose tolerance, and eventually develop diabetes. Although their insulin levels are elevated, they present lower insulin output in response to glucose than obese individuals. Rodent models demonstrate that GC-induced IR is accompanied by compensatory beta-cell hyperplasia. GC excess with high-fat diet leads to fasting hyperglycaemia and suppressed glucose-stimulated insulin secretion (GSIS) despite increased beta cell mass.
The majority of in vitro studies confirm an inhibitory GC effect on insulin secretion. The mechanism remains ambiguous but might involve its direct influence upon expression of molecules essential for glucose sensing and metabolism, enhanced glucose cycling, down-regulated insulin gene transcription, hampered insulin exocytosis, amplified alpha-adrenergic signalling, and/or increased beta-cell apoptosis. There are also reports that suggest increased GSIS after beta cell exposure to GCs in vitro. Transgenic mice with enhanced corticosterone regeneration within their beta cells present augmented secretory capacity of their islets.
To summarise, GCs exert a significant role in carbohydrate balance through various mechanisms, including direct impact on beta cell function. Observed discrepancies may arise from differences in study design. A thorough understanding of GC action will provide important clinical clues for disorders of glucose homeostasis.
Keywords: glucocorticoidsbeta cellinsulin
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