The control of insulin secretion by adipokines: current evidence for adipocyte-beta cell endocrine signalling in metabolic homeostasis

Abstract

Metabolic homeostasis is maintained by the coordinated action of multiple organ systems. Insulin secretion is often enhanced during obesity or insulin resistance to maintain glucose and lipid homeostasis, whereas a loss of insulin secretion is associated with type 2 diabetes. Adipocytes secrete hormones known as adipokines which act on multiple cell types to regulate metabolism. Many adipokines have been shown to influence beta cell function by enhancing or inhibiting insulin release or by influencing beta cell survival. Insulin, in turn, regulates lipolysis and promotes glucose uptake and lipid storage in adipocytes. As adipokine secretion and action is strongly influenced by obesity, this provides a potential route by which beta cell function is coordinated with adiposity, independently of alterations in blood glucose or lipid levels. In this review, I assess the evidence for the direct regulation of beta cell function by the adipokines leptin, adiponectin, extracellular nicotinamide phosphoribosyltransferase, apelin, resistin, retinol binding protein 4, fibroblast growth factor 21, nesfatin-1 and fatty acid binding protein 4. I summarise in vitro and in vivo data and discuss the influence of obesity and diabetes on circulating adipokine concentrations, along with the potential for influencing beta cell function in human physiology. Finally, I highlight future research questions that are likely to yield new insights into the exciting field of insulinotropic adipokines.

Dysregulated homeostatic pathways in sarcopenia among frail older adults

“…This is negatively linked to ISEM, consistent with the known influence of adipokines on beta cell function through enhancing or inhibiting insulin release (Cantley, 2014), pointing to the dysregulated production of adipokines in sarcopenia associated with obesity.…”

The Prevention and Treatment of Type 2 Diabetes Mellitus with a Plant-Based Diet

“…The adipose tissue is an important endocrine organ that plays a key role in the integration of endocrine, metabolic, and inflammatory signals for the control of energy homeostasis [41]. In addition to the dysregulation of its free fatty acid buffering capacity, [42] the adipocyte has been shown to secrete a variety of bioactive proteins into the circulation. These secretory proteins have been collectively named adipocytokines [41].…”

“…Although adiponectin is secreted only from adipose tissue, its levels are paradoxically lower in obese than in lean humans [52][53][54][55][56][57][58]. A strong correlation between adiponectin and systemic insulin sensitivity has been well established both in vivo and in vitro in mice, other laboratory animals, and, most importantly, humans [41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59]. In humans, plasma levels of adiponectin are significantly lower in insulinresistant states including T2DM [52][53][54][55][56][57][58].…”

Preventing Long-Term Complications of Obesity, Type 2 Diabetes, and Metabolic Syndrome

“…Most of these cytokines liberated from the hyperactive, enlarge fat cells are inflammatogenic, promoting insulin resistance, inflammation, and atherosclerosis [47][48][49]. In persons with visceral obesity, the synthesis and secretion of protective cytokines such as leptin and adiponectin are significantly reduced [14, 50,51].…”