Amylin dual action: a second gluco regulatory β-cell hormone, treatment and cause for the diabetes

The role of external ATP for intercellular communication was studied in glucose-stimulated pancreatic β-cells isolated from ob/ob mice. Digital image analyses with fura-2 revealed spontaneous transients of cytoplasmic Ca2+ appearing in synchrony in the absence of cell contacts. After removal of slow oscillations with methoxyverapamil, addition of ATP (0.1–100 μM) resulted in prompt firing of a transient, followed by suppression of the generation and synchronization of spontaneously occurring transients. It was possible to trigger transients during the suppressive phase by raising the concentration of ATP. The dual action of ATP was mimicked by ADP or 2-methylthio-ATP but not by AMP or UTP. The number of spontaneous transients and their synchronization were reduced in the presence of the dephosphorylating agent apyrase. Additional evidence that intermittent release of ATP participates in the generation of spontaneous Ca2+ transients was obtained from the suppression observed from use of antagonists of the purinoceptors [suramin (0.3–30 μM), pyridoxalphosphate-6-azophenyl-2,4-disulfonic acid (PPADS; 10–30 μM) and 2-deoxy- N-methyladenosine (MRS 2179; 0.3–30 μM)] or from counteracting β-cell release of ATP by inhibiting exocytosis with 100 nM epinephrine, 100 nM somatostatin, or lowering the temperature below 30°C. The data indicate that ATP has time-dependent actions (prompt stimulation followed by inhibition) on the generation of Ca2+ transients mediated by P2Y receptors. It is proposed that β-cells both receive a neural ATP signal with coordinating effects on their Ca2+ oscillations and propagate this message to adjacent cells via intermittent release of ATP combined with gap junction coupling.

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Nicotinamide Mononucleotide Prevents Free Fatty Acid-Induced Reduction in Glucose Tolerance by Decreasing Insulin Clearance

International Journal of Molecular Sciences ◽

10.3390/ijms222413224 ◽

2021 ◽

Vol 22 (24) ◽

pp. 13224

Author(s):

Ashraf Nahle ◽

Yemisi Deborah Joseph ◽

Sandra Pereira ◽

Yusaku Mori ◽

Frankie Poon ◽

...

Keyword(s):

Glucose Tolerance ◽

Glucose Intolerance ◽

Cell Function ◽

Insulin Clearance ◽

Β Cell ◽

Cell Dysfunction ◽

Nicotinamide Mononucleotide ◽

Nad Synthesis ◽

Β Cell Function ◽

Dual Action

The NAD-dependent deacetylase SIRT1 improves β cell function. Accordingly, nicotinamide mononucleotide (NMN), the product of the rate-limiting step in NAD synthesis, prevents β cell dysfunction and glucose intolerance in mice fed a high-fat diet. The current study was performed to assess the effects of NMN on β cell dysfunction and glucose intolerance that are caused specifically by increased circulating free fatty acids (FFAs). NMN was intravenously infused, with or without oleate, in C57BL/6J mice over a 48-h-period to elevate intracellular NAD levels and consequently increase SIRT1 activity. Administration of NMN in the context of elevated plasma FFA levels considerably improved glucose tolerance. This was due not only to partial protection from FFA-induced β cell dysfunction but also, unexpectedly, to a significant decrease in insulin clearance. However, in conditions of normal FFA levels, NMN impaired glucose tolerance due to decreased β cell function. The presence of this dual action of NMN suggests caution in its proposed therapeutic use in humans.

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Adiposity in Children Born Small for Gestational Age Is Associated With β-Cell Function, Genetic Variants for Insulin Resistance, and Response to Growth Hormone Treatment

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2015-3019 ◽

2016 ◽

Vol 101 (1) ◽

pp. 131-142 ◽

Cited By ~ 5

Author(s):

Ajay Thankamony ◽

Rikke Beck Jensen ◽

Susan M. O'Connell ◽

Felix Day ◽

Jeremy Kirk ◽

...

Keyword(s):

Insulin Resistance ◽

Growth Hormone ◽

Gestational Age ◽

Small For Gestational Age ◽

Genetic Variants ◽

Growth Hormone Treatment ◽

Cell Function ◽

Hormone Treatment ◽

Β Cell ◽

Β Cell Function

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Adipokines as key players in β cell function and failure

Clinical Science ◽

10.1042/cs20190523 ◽

2019 ◽

Vol 133 (22) ◽

pp. 2317-2327 ◽

Cited By ~ 3

Author(s):

Nicolás Gómez-Banoy ◽

James C. Lo

Keyword(s):

Metabolic Diseases ◽

Cell Function ◽

Whole Body ◽

Pancreatic Β Cell ◽

Β Cell ◽

Cell Axis ◽

Β Cell Function ◽

Prevalence Of Obesity ◽

Specific Factors ◽

Whole Body Metabolism

Abstract The growing prevalence of obesity and its related metabolic diseases, mainly Type 2 diabetes (T2D), has increased the interest in adipose tissue (AT) and its role as a principal metabolic orchestrator. Two decades of research have now shown that ATs act as an endocrine organ, secreting soluble factors termed adipocytokines or adipokines. These adipokines play crucial roles in whole-body metabolism with different mechanisms of action largely dependent on the tissue or cell type they are acting on. The pancreatic β cell, a key regulator of glucose metabolism due to its ability to produce and secrete insulin, has been identified as a target for several adipokines. This review will focus on how adipokines affect pancreatic β cell function and their impact on pancreatic β cell survival in disease contexts such as diabetes. Initially, the “classic” adipokines will be discussed, followed by novel secreted adipocyte-specific factors that show therapeutic promise in regulating the adipose–pancreatic β cell axis.

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