Pharmacological mechanisms of hormone action in hypoglycemia: Maintaining glucose balance
Received: 31-May-2023, Manuscript No. ajdm-23-104708; Editor assigned: 02-Jun-2023, Pre QC No. ajdm-23-104708 (PQ); Reviewed: 16-Jun-2023, QC No. ajdm-23-104708; Revised: 21-Jun-2023, Manuscript No. ajdm-23-104708 (R); Published: 28-Jun-2023, DOI: 10.54931/AJDM-31.3.8.
Hypoglycemia, characterized by abnormally low blood glucose levels, is a critical condition that requires prompt intervention. Hormones play a crucial role in glucose regulation, and pharmacological agents targeting these hormonal pathways are essential in managing hypoglycemia. In this article, we explore the pharmacological mechanisms of hormone action involved in countering hypoglycemia, focusing on glucagon, epinephrine, and cortisol.
Glucagon, produced by the alpha cells in the pancreatic islets, acts as a counter-regulatory hormone to insulin. In the context of hypoglycemia, glucagon plays a pivotal role in increasing blood glucose levels. Glucagon stimulates hepatic glycogenolysis, the breakdown of glycogen stored in the liver, and promotes gluconeogenesis, the synthesis of glucose from non-carbohydrate sources.
Pharmacological agents known as glucagon receptor agonists, such as glucagon-like peptide-1 receptor agonists, mimic the action of glucagon. These agents activate the glucagon receptor, stimulating hepatic glucose production and release. GLP-1 receptor agonists, in addition to their glucose-lowering effects in diabetes management, have demonstrated efficacy in treating hypoglycemia in certain clinical settings. Epinephrine, also known as adrenaline, is a hormone released from the adrenal glands in response to stress or low blood glucose levels. It acts on various tissues, including the liver, muscles, and adipose tissue, to raise blood glucose levels during hypoglycemia. Epinephrine promotes glycogenolysis and gluconeogenesis in the liver, similar to glucagon. Additionally, it enhances the breakdown of glycogen in skeletal muscles, releasing glucose into the bloodstream. Epinephrine also inhibits insulin release from pancreatic beta cells, further preventing excessive glucose uptake and utilization.
In emergency situations of severe hypoglycemia, the administration of exogenous epinephrine, such as through an auto-injector, can rapidly raise blood glucose levels. This intervention is particularly important for individuals with adrenal insufficiency or impaired counter-regulatory hormone responses. Cortisol, known as the stress hormone, is a glucocorticoid released from the adrenal glands. It plays a significant role in glucose metabolism, particularly during periods of stress or fasting. Cortisol helps maintain blood glucose levels by promoting gluconeogenesis in the liver, inhibiting glucose uptake in peripheral tissues, and stimulating lipolysis, the breakdown of stored fats, to provide an alternative energy source. In pharmacological management of hypoglycemia, synthetic glucocorticoids, such as hydrocortisone, can be administered to enhance cortisol action. These agents mimic the effects of endogenous cortisol and facilitate glucose production and release from the liver.
Pharmacological agents targeting the hormonal mechanisms involved in hypoglycemia management play a vital role in restoring and maintaining glucose balance. Glucagon, epinephrine, and cortisol act as crucial counter-regulatory hormones, promoting hepatic glucose production, inhibiting excessive glucose uptake, and stimulating alternative energy sources.
Over the past decades, numerous studies on podocytes exposed to high-glucose environments have shown that hyperglycemia can alter podocyte phenotype by inducing loss of nephrin and alterations in the production/degradation of extracellular matrix components proved to be viable. A decrease in nephron number due to low nephron mass/nephron loss results in a compensatory increase in glomerular capillary pressure/filtration of the remaining single nephron. This leaves the total glomerular filtration rate unchanged for long periods, but causes podocyte damage, representing an important mechanism in CKD progression. Also, in obesity and diabetes, both glomerular capillary hypertension and single-nephron hyper-filtration are early events that precede nephron loss.