Nutrient regulation of insulin secretion and action

Abstract

Pancreatic b-cell function is of critical importance in the regulation of fuel homoeostasis, and metabolic dysregulation is a hallmark of diabetes mellitus (DM). The b-cell is an intricately designed cell type that couples metabolism of dietary sources of carbohydrates, amino acids and lipids to insulin secretory mechanisms, such that insulin release occurs at appropriate times to ensure efficient nutrient uptake and storage by target tissues. However, chronic exposure to high nutrient concentrations results in altered metabolism that impacts negatively on insulin exocytosis, insulin action and may ultimately lead to development of DM. Reduced action of insulin in target tissues is associated with impairment of insulin signalling and contributes to insulin resistance (IR), a condition often associated with obesity and a major risk factor for DM. The altered metabolism of nutrients by insulin-sensitive target tissues (muscle, adipose tissue and liver) can result in high circulating levels of glucose and various lipids, which further impact on pancreatic b-cell function, IR and progression of the metabolic syndrome. Here, we have considered the role played by the major nutrient groups, carbohydrates, amino acids and lipids, in mediating b-cell insulin secretion, while also exploring the interplay between amino acids and insulin action in muscle. We also focus on the effects of altered lipid metabolism in adipose tissue and liver resulting from activation of inflammatory processes commonly observed in DM pathophysiology. The aim of this review is to describe commonalities and differences in metabolism related to insulin secretion and action, pertinent to the development of DM.

The Pancreatic β-Cell: A Bioenergetic Perspective

“…There are several excellent reviews of the current consensus of the mechanisms operative in the ␤-cell that couple oxidative metabolism to insulin secretion (220,255,369,420,452,460), so what is the purpose of the current contribution, particularly since it is written by an observer external to the field? The review is a response to the difficulties that this mitochondrial physiologist has encountered in trying to understand the ␤-cell literature in the same way as one would approach the liver, muscle, or adipose tissue.…”

Lactisole inhibits the glucose-sensing receptor T1R3 expressed in mouse pancreatic β-cells

“…Glucose is a primary stimulator of insulin secretion in pancreatic b-cells and modulates the effects of incretins and acetylcholine (Ashcroft & Rorsman 1989, Rasmussen et al 1990, Rorsman 1997, Newsholme et al 2014. We have shown recently that T1R3, a subunit of the sweet taste receptor (Nelson et al 2001, Temussi 2007, functions as a glucose-sensing receptor in b-cells (Malaisse 2014, Kojima et al 2015.…”

Physiological regulation of the heat shock response by glutamine: implications for chronic low-grade inflammatory diseases in age-related conditions

“…Indeed, ROS production by normal metabolism and its overproduction in inflamed states are direct causes of aging and many aging-related degenerative complications [147]. This may be because levels of ROS during aging can increase due to a limited capacity of antioxidant systems and repair mechanisms [148]. Thus, excessive ROS production and the impaired resistance against oxidative stress, as well as a defective HS response capacity (which could alleviate ROS consequences) have been proposed to play a major role to accelerate aging process [140].…”

“…However, despite directly causal factors, the establishment of sarcopenia is closely related to inflammatory processes and aggravated by the concomitant age-related changes in cytoprotective mechanisms (particularly those involving protein quality control) [29]. In any way, all the above conditions surrounding sarcopenia tend to limit physical activity which, in turn, predisposes the elderly to chronic inflammatory diseases, including obesities and T2DM [13,148].…”