In situ activation of the type 2 ryanodine receptor in pancreatic beta cells requires cAMP-dependent phosphorylation

In the present study, we have examined the origin and growth pattern of the beta cells in pancreatic islets, to determine whether a single progenitor cell gave rise to all the precursors of the islets, or if each of a few progenitor cells is the founder of a different islet, or if each islet is a mixture of cells originating from a pool of progenitor cells. Aggregation mouse chimaeras where the pancreatic beta cells derived from each embryo can be identified in the islets on histological sections were analyzed. In two chimaeras, all the islets contained cells from both the aggregated embryo. This clearly demonstrates that each islet resulted from several independent cells. In addition, the beta cells derived from either embryo component were in very small clusters in the islets, suggesting that in situ cell division did not account significantly for islet growth.

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Disruption of Beta-Cell Mitochondrial Networks by the Orphan Nuclear Receptor Nor1/Nr4a3

Cells ◽

10.3390/cells9010168 ◽

2020 ◽

Vol 9 (1) ◽

pp. 168 ◽

Cited By ~ 2

Author(s):

Anne-Françoise Close ◽

Nidheesh Dadheech ◽

Hélène Lemieux ◽

Qian Wang ◽

Jean Buteau

Keyword(s):

Beta Cell ◽

Beta Cells ◽

Nuclear Receptor ◽

Pancreatic Beta Cells ◽

Orphan Nuclear Receptor ◽

Atp Production ◽

Human Beta Cells ◽

Glucose Stimulated Insulin Secretion ◽

Mitochondrial Networks

Nor1, the third member of the Nr4a subfamily of nuclear receptor, is garnering increased interest in view of its role in the regulation of glucose homeostasis. Our previous study highlighted a proapoptotic role of Nor1 in pancreatic beta cells and showed that Nor1 expression was increased in islets isolated from type 2 diabetic individuals, suggesting that Nor1 could mediate the deterioration of islet function in type 2 diabetes. However, the mechanism remains incompletely understood. We herein investigated the subcellular localization of Nor1 in INS832/13 cells and dispersed human beta cells. We also examined the consequences of Nor1 overexpression on mitochondrial function and morphology. Our results show that, surprisingly, Nor1 is mostly cytoplasmic in beta cells and undergoes mitochondrial translocation upon activation by proinflammatory cytokines. Mitochondrial localization of Nor1 reduced glucose oxidation, lowered ATP production rates, and inhibited glucose-stimulated insulin secretion. Western blot and microscopy images revealed that Nor1 could provoke mitochondrial fragmentation via mitophagy. Our study unveils a new mode of action for Nor1, which affects beta-cell viability and function by disrupting mitochondrial networks.

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Guesstimate Probable Partial Recovery of Pancreatic Beta Cells Using Calculations of Annualized Fasting Plasma Glucose Decreased Amount (GH-Method: mathphysical medicine)

Medical & Clinical Research ◽

10.33140/mcr.05.05.01 ◽

2020 ◽

Vol 5 (5) ◽

Keyword(s):

Type 2 Diabetes ◽

Body Weight ◽

Beta Cells ◽

Plasma Glucose ◽

Fasting Plasma Glucose ◽

Pancreatic Beta Cells ◽

Partial Recovery ◽

Fasting Plasma ◽

Regeneration Capability

In this paper, the author describes his hypothesis on the probable partial self-recovery of some insulin regeneration capability of pancreatic beta cells on a type 2 diabetes (T2D) patient via his collected data of fasting plasma glucose (FPG) and body weight during the period of 1/1/2014 to 11/2/2019.

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Beta Cell Autophagy in the Pathogenesis of Type 1 Diabetes

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00151.2021 ◽

2021 ◽

Author(s):

Charanya Muralidharan ◽

Amelia K Linnemann

Keyword(s):

Type 1 Diabetes ◽

Beta Cell ◽

Beta Cells ◽

Pancreatic Beta Cells ◽

Potential Role ◽

Cell Dysfunction ◽

Unconventional Secretion ◽

Insulin Dependent

Type 1 diabetes is an insulin-dependent, autoimmune disease where the pancreatic beta cells are destroyed resulting in hyperglycemia. This multi-factorial disease involves multiple environmental and genetic factors, and has no clear etiology. Accumulating evidence suggests that early signaling defects within the beta cells may promote a change in the local immune mileu, contributing to autoimmunity. Therefore, many studies have been focused on intrinsic beta cell mechanisms that aid in restoration of cellular homeostasis under environmental conditions that cause dysfunction. One of these intrinsic mechanisms to promote homeostasis is autophagy, defects in which are clearly linked with beta cell dysfunction in the context of type 2 diabetes. Recent studies have now also pointed towards beta cell autophagy defects in the context of type 1 diabetes. In this perspectives review, we will discuss the evidence supporting a role for beta cell autophagy in the pathogenesis of type 1 diabetes, including a potential role for unconventional secretion of autophagosomes/lysosomes in the changing dialogue between the beta cell and immune cells.

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