Incretin Hormones: Key Players in Glucose Homeostasis and Beyond

Rajak Ahmed^*
*Correspondence: Rajak Ahmed, Department of Medicinal Chemistry, Banaras Hindu University, Varanasi, India, Email:

Introduction

Incretin hormones play a crucial role in regulating glucose homeostasis and are gaining significant attention in the field of metabolic research. These hormones are secreted from the gastrointestinal tract in response to nutrient intake, and their effects on insulin secretion and glucose metabolism have made them promising targets for the treatment of diabetes and metabolic disorders. In this article, we will explore the biology of incretin hormones, their physiological functions, therapeutic implications, and potential future directions for research. Incretin hormones are a group of peptide hormones secreted by the gastrointestinal tract in response to nutrient intake. The two major incretin hormones are Glucagon-Like Peptide-1 (GLP-1) and Glucose-Dependent Insulinotropic Polypeptide (GIP). These hormones play a crucial role in glucose homeostasis by regulating insulin and glucagon secretion, delaying gastric emptying, and promoting satiety. Their effects on glucose metabolism have made them attractive therapeutic targets for the treatment of diabetes and related metabolic disorders [1].

Incretin hormones are primarily secreted by specialized enteroendocrine cells located in the intestinal mucosa. The secretion of incretin hormones is regulated by a complex interplay of neural, hormonal, and metabolic factors. The gut-brain axis, involving signals from the central nervous system and the enteric nervous system, plays a crucial role in modulating incretin hormone secretion. Additionally, nutrients such as glucose, fatty acids, and amino acids directly stimulate incretin hormone release. GLP-1 and GIP exert their effects on glucose metabolism through various mechanisms. GLP-1 stimulates glucose-dependent insulin secretion, meaning that it enhances insulin release when blood glucose levels are high and suppresses it when glucose levels are low, thereby reducing the risk of hypoglycemia. GLP-1 also inhibits glucagon secretion, which helps to lower blood glucose levels. Furthermore, incretin hormones delay gastric emptying, leading to a slower absorption of nutrients and a more gradual rise in postprandial glucose levels. These effects collectively contribute to improved glycemic control [2].

The therapeutic potential of incretin hormones and their analogs has led to the development of several classes of drugs for the treatment of diabetes. GLP-1 receptor agonists and Dipeptidyl Peptidase-4 (DPP-4) inhibitors are two major classes of drugs that target the GLP-1 pathway. GLP-1 receptor agonists, administered as injectables, provide sustained GLP-1 receptor activation and have shown significant efficacy in improving glycemic control and promoting weight loss. DPP-4 inhibitors, on the other hand, inhibit the enzymatic degradation of endogenous GLP-1, thereby increasing its half-life and enhancing its effects. Dual incretin receptor agonists and GIP receptor modulators are emerging as potential future options for incretin-based therapies. In addition to their glycemic effects, incretin hormones have demonstrated various non-glycemic benefits. GLP-1 receptor agonists have shown cardiovascular benefits by reducing the risk of major adverse cardiovascular events in patients with type 2 diabetes. GLP-1 has also been implicated in neuroprotective effects, with potential implications for neurodegenerative diseases such as Alzheimer's and Parkinson's. Furthermore, GLP-1 and GIP have anti-inflammatory actions and have been linked to improved markers of inflammation. These multifaceted effects of incretin hormones expand their therapeutic potential beyond glycemic control.

Description

Despite the success of incretin-based therapies, several challenges and opportunities exist. Long-term safety and efficacy data are still being gathered, and further research is needed to fully understand the potential risks and benefits associated with these therapies. Personalized medicine approaches, considering individual patient characteristics and genetics, may help optimize treatment outcomes. Additionally, combining different classes of incretin-based therapies or targeting multiple receptor pathways simultaneously (polypharmacology) could be explored to enhance therapeutic efficacy. Moreover, novel approaches for incretin hormone activation, such as gene therapy and targeted delivery systems, hold promise for future advancements. Incretin hormones play a pivotal role in glucose homeostasis, and their therapeutic potential extends beyond glycemic control. GLP-1 and GIP have emerged as key players in the treatment of diabetes and metabolic disorders, offering benefits such as improved glycemic control, weight loss, cardiovascular protection and potential neuroprotective effects [3].

As research in this field continues to advance, incretin-based therapies hold great promise for the future of diabetes management and the treatment of various metabolic disorders, paving the way for more effective and personalized treatment strategies. In addition to their glucose-lowering effects, incretin hormones have shown cardiovascular benefits. Clinical trials with GLP-1 receptor agonists have demonstrated a reduction in major adverse cardiovascular events, including cardiovascular death, nonfatal myocardial infarction, and stroke, in patients with type 2 diabetes and a high cardiovascular risk. The mechanisms underlying these benefits are not fully understood but may involve improvements in endothelial function, reduction in systemic inflammation, and direct actions on the cardiovascular system. These findings have positioned GLP-1 receptor agonists as an attractive therapeutic option for individuals with diabetes and cardiovascular comorbidities. Emerging evidence suggests that incretin hormones, particularly GLP-1, may have neuroprotective effects. Preclinical studies have shown that GLP-1 receptor activation can promote neuronal survival, enhance synaptic plasticity, and reduce neuroinflammation.

These effects have raised interest in the potential use of GLP-1-based therapies for neurodegenerative diseases such as Alzheimer's and Parkinson's. Clinical trials investigating the effects of GLP-1 receptor agonists on cognitive function and neurodegenerative biomarkers are currently underway, providing insights into the therapeutic potential of incretin hormones in these conditions. Incretin hormones have been implicated in modulating inflammation. GLP- 1 and GIP receptors are expressed in various immune cells, including macrophages and lymphocytes. Activation of these receptors has been shown to reduce the production of pro-inflammatory cytokines and promote an antiinflammatory environment. In experimental models, GLP-1 receptor agonists have demonstrated attenuation of inflammation in various tissues, including the liver, adipose tissue, and blood vessels. These anti-inflammatory actions may contribute to the cardiovascular and metabolic benefits observed with incretin-based therapies [4].

In addition to their effects on glucose metabolism, incretin hormones have implications for obesity management. GLP-1 receptor agonists have consistently been associated with weight loss in clinical trials. The mechanisms underlying this weight loss include increased satiety, delayed gastric emptying, and reduced food intake. GLP-1 receptor agonists also exert central effects on appetite regulation by acting on the hypothalamus. These properties make GLP-1 receptor agonists a valuable therapeutic option for individuals with obesity and type 2 diabetes, where weight management is a crucial aspect of treatment [5].

Conclusion

Incretin hormones, particularly GLP-1 and GIP, have emerged as critical regulators of glucose homeostasis with broad implications for the treatment of diabetes and metabolic disorders. Their effects extend beyond glycemic control, encompassing cardiovascular benefits, neuroprotective effects, anti-inflammatory actions, and weight management properties. Incretinbased therapies, including GLP-1 receptor agonists and DPP-4 inhibitors, have shown significant efficacy in clinical trials. However, ongoing research is necessary to address long-term safety concerns, explore non-glycemic effects, and optimize treatment strategies through personalized medicine and combination therapies. The future of incretin hormone research holds promise for advancements in the management of diabetes and metabolic disorders, offering novel therapeutic avenues for improved patient outcomes.

Acknowledgement

None.

Conflict of Interest

None.

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