The Interplay of Adipokines and Pancreatic Beta Cells in Metabolic Regulation and Diabetes

Abstract

The interplay between adipokines and pancreatic beta cells, often referred to as the adipo-insular axis, plays a crucial role in regulating metabolic homeostasis. Adipokines are signaling molecules secreted by adipocytes that have profound effects on several physiological processes. Adipokines such as adiponectin, leptin, resistin, and visfatin influence the function of pancreatic beta cells. The reciprocal communication between adipocytes and beta cells is remarkable. Insulin secreted by beta cells affects adipose tissue metabolism, influencing lipid storage and lipolysis. Conversely, adipokines released from adipocytes can influence beta cell function and survival. Chronic obesity and insulin resistance can lead to the release of excess fatty acids and inflammatory molecules from the adipose tissue, contributing to beta cell dysfunction and apoptosis, which are key factors in developing type 2 diabetes. Understanding the complex interplay of the adipo-insular axis provides insights into the mechanisms underlying metabolic regulation and pathogenesis of metabolic disorders. By elucidating the molecular mediators involved in this interaction, new therapeutic targets and strategies may emerge to reduce the risk and progression of diseases, such as type 2 diabetes and its associated complications. This review summarizes the interactions between adipokines and pancreatic beta cells, and their roles in the pathogenesis of diabetes and metabolic diseases.

Strengthening the Evidence for a Causal Link between Type 2 Diabetes Mellitus and Pancreatic Cancer: Insights from Two-Sample and Multivariable Mendelian Randomization

“…The pathophysiological mechanisms linking T2DM to PaCa are complex and multifaceted, encompassing insulin resistance and hyperinsulinemia [16,[36][37][38], persistent hyperglycemia [39][40][41][42], chronic inflammation [16,43,44], alterations in gut microbiota [45][46][47][48][49], and dysregulated adipokine secretion [16,[50][51][52][53][54]. Insulin resistance in T2DM leads to hyperinsulinemia, potentially promoting tumor growth directly by acting on insulin receptors or indirectly by increasing levels of insulin-like growth factor-1 (IGF-1), both of which can stimulate cell proliferation and inhibit apoptosis to enhance cell proliferation pathways [36][37][38].…”

“…Changes in the gut microbiota related to T2DM may influence systemic inflammation and metabolic profiles, which may affect cancer development through alterations in bile acid metabolism and the release of metabolites that may have carcinogenic properties [45][46][47][48][49]. Moreover, altered adipokine secretion, characterized by increased leptin and decreased adiponectin levels due to adiposity in T2DM, may facilitate cancer progression through pro-inflammatory and anti-apoptotic effects [50][51][52][53][54]. These interconnected pathways underscore the complex relationship between T2DM and PaCa.…”

New Mediators in the Crosstalk between Different Adipose Tissues

“…In fact, it has been demonstrated that WAT can secrete approximately more than fifty different signaling molecules and hormones, namely adipokines [22], which play a relevant role in the metabolism of glucose and immunity. Changes in its secretion profile may contribute to insulin and leptin resistance and induce the development of obesity and T2D [23,24], whereas it has been observed that the adipose tissue of lean individuals predominantly secretes anti-inflammatory adipokines such as transforming growth factor-beta (TGF β), adiponectin, apelin, IL-4, IL-10, and IL-13 [25].…”

“…Cytokines secreted by WAT, such as TNF-α, IL-6, IL-1β, IL-8, or IL-18, are implicated in inflammatory processes [25] and disrupted adipokine production and secretion are strongly associated with obesity-related comorbidities [24]. In this sense, resistin seems to be involved in insulin resistance and inflammation in humans and murine models [30].…”

Influence on polymorphism of visfatin (rs 4730153) and nesfatin (rs 1330) genes on the development of the metabolic syndrome

“…However, its greatest importance is its hypoglycaemic effect. It stimulates insulin secretion, improves pancreatic beta-cell function, and modulates the expression of genes involved in maintaining glucose homeostasis [7].…”