Pancreatic islet cells: A model for calcium‐dependent peptide release

Abstract

In mammals the concentration of blood glucose is kept close to 5 mmol∕l. Different cell types in the islet of Langerhans participate in the control of glucose homeostasis. β-cells, the most frequent type in pancreatic islets, are responsible for the synthesis, storage, and release of insulin. Insulin, released with increases in blood glucose promotes glucose uptake into the cells. In response to glucose changes, pancreatic α-, β-, and δ-cells regulate their electrical activity and Ca(2+) signals to release glucagon, insulin, and somatostatin, respectively. While all these signaling steps are stimulated in hypoglycemic conditions in α-cells, the activation of these events require higher glucose concentrations in β and also in δ-cells. The stimulus-secretion coupling process and intracellular Ca(2+) ([Ca(2+)](i)) dynamics that allow β-cells to secrete is well-accepted. Conversely, the mechanisms that regulate α- and δ-cell secretion are still under study. Here, we will consider the glucose-induced signaling mechanisms in each cell type and the mathematical models that explain Ca(2+) dynamics.

Distinct Initial SNARE Configurations Underlying the Diversity of Exocytosis

“…The pancreas, or pancreatic islets, contain three types of endocrine cell: ␣ cells (which secrete glucagon), ␤ cells (which secrete insulin), and ␦ cells (which secrete somatostatin). An increase in [Ca 2ϩ ] i is the major trigger for secretion in all three cell types (248,505,609,693,700). ␤ cells form the major cell mass in the islets, and insulin secretion is of crucial importance to health and disease as it is the only hormone that facilitates glucose uptake by muscle and adipocytes, leading to a reduction in blood glucose levels.…”

Protein transamidation by transglutaminase 2 in cells: a disputed Ca2+‐dependent action of a multifunctional protein

“…In pancreatic islet cells stimulus‐secretion coupling by glucose addition, which leads to TG2 activation and protein serotonylation [76] as discussed in the review in this issue by Walther et al. [58], generates Ca 2+ microgradients that reach values of 8–10 μ m beneath the plasma membrane, and even higher ones in the nucleoplasm [77]. These levels of Ca 2+ concentration are well above the 3–4 μ m needed for switching on transamidase activity of even a purified TG2 [21].…”

The Glycolytic Pathway is the Predominate Path for Glucose Utilization in Human Pancreatic Beta Cells (1.1B4)

“…The same principle would be suggested to explain the differences between highly content glucokinase mouse islet EC50 = 8 mM (Panten and Klein, 1982) in one hand and murine cell line MIN6 on the other hand. Since both of 1.1B4 and beta cells from pancreatic islet depend on glucokinase activity, therefore 1.1B4 had a comparable EC50 of MTS reduction with human pancreatic islets (EC50 =12 mM) found by Panten and Klein (1982) and Soria et al (2010).…”