The Role of TRP Channels in the Pancreatic Beta-Cell

The pancreatic beta-cell transduces the availability of nutrients into the secretion of insulin. While this process is extensively modified by hormones and neurotransmitters, it is the availability of nutrients, above all glucose, which sets the process of insulin synthesis and secretion in motion. The central role of the mitochondria in this process was identified decades ago, but how changes in mitochondrial activity are coupled to the exocytosis of insulin granules is still incompletely understood. The identification of ATP-sensitive K+-channels provided the link between the level of adenine nucleotides and the electrical activity of the beta cell, but the depolarization-induced Ca2+-influx into the beta cells, although necessary for stimulated secretion, is not sufficient to generate the secretion pattern as produced by glucose and other nutrient secretagogues. The metabolic amplification of insulin secretion is thus the sequence of events that enables the secretory response to a nutrient secretagogue to exceed the secretory response to a purely depolarizing stimulus and is thus of prime importance. Since the cataplerotic export of mitochondrial metabolites is involved in this signaling, an orienting overview on the topic of nutrient secretagogues beyond glucose is included. Their judicious use may help to define better the nature of the signals and their mechanism of action.

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Pancreatic beta-cell electrical activity: the role of anions and the control of pH

AJP Cell Physiology ◽

10.1152/ajpcell.1983.244.3.c188 ◽

1983 ◽

Vol 244 (3) ◽

pp. C188-C197 ◽

Cited By ~ 31

Author(s):

G. T. Eddlestone ◽

P. M. Beigelman

Keyword(s):

Membrane Potential ◽

Cell Membrane ◽

Beta Cell ◽

Pancreatic Beta Cell ◽

Proton Exchange ◽

Disulfonic Acid ◽

Control Mechanisms ◽

Exchange System ◽

Sodium Proton Exchange

The influence of chloride on the mouse pancreatic beta-cell membrane potential and the cell membrane mechanisms controlling intracellular pH (pHi) have been investigated using glass microelectrodes to monitor the membrane potential. It has been shown that chloride is distributed passively across the beta-cell membrane such that chloride potential is equal to the membrane potential. Withdrawal of perifusate chloride or bicarbonate and the application of the drugs 4-acetamido-4'-isethiocyanostilbene-2,2'-disulfonic acid (SITS) and probenecid, both blockers of transmembrane anion movement, have been used to establish that a chloride-bicarbonate exchange system is operative in the cell membrane and that it is one of the control mechanisms of pHi. Amiloride, a specific blocker of the transmembrane sodium proton exchange, has been used to demonstrate that this mechanism is also operative in the beta-cell membrane in the control of pHi. The hypothesis that the calcium-activated potassium permeability is proton sensitive at an intracellular site, a fall in pHi causing a fall in permeability and an increase in pHi causing an increase in permeability, has been used to explain many of the effects observed in this study.

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Incretin Receptor Null Mice Reveal Key Role of GLP-1 but Not GIP in Pancreatic Beta Cell Adaptation to Pregnancy

PLoS ONE ◽

10.1371/journal.pone.0096863 ◽

2014 ◽

Vol 9 (6) ◽

pp. e96863 ◽

Cited By ~ 32

Author(s):

R. Charlotte Moffett ◽

Srividya Vasu ◽

Bernard Thorens ◽

Daniel J. Drucker ◽

Peter R. Flatt

Keyword(s):

Beta Cell ◽

Pancreatic Beta Cell ◽

Cell Adaptation ◽

Beta Cell Adaptation

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W46 ROLE OF LIPOPROTEINS IN PANCREATIC BETA-CELL SURVIVAL, PROLIFERATION AND FUNCTION

Atherosclerosis Supplements ◽

10.1016/s1567-5688(10)70047-7 ◽

2010 ◽

Vol 11 (2) ◽

pp. 10

Author(s):

R.A. Sibler ◽

S. Rütti ◽

J.A. Ehses ◽

R. Prazak ◽

D.T. Meier ◽

...

Keyword(s):

Beta Cell ◽

Cell Survival ◽

Pancreatic Beta Cell ◽

And Function

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The role of Raf-1 kinase inhibitor protein in the regulation of pancreatic beta cell proliferation in mice

Diabetologia ◽

10.1007/s00125-012-2696-9 ◽

2012 ◽

Vol 55 (12) ◽

pp. 3331-3340 ◽

Cited By ~ 7

Author(s):

F. N. Pardo ◽

J. Altirriba ◽

M. Pradas-Juni ◽

A. García ◽

U. Ahlgren ◽

...

Keyword(s):

Cell Proliferation ◽

Beta Cell ◽

Kinase Inhibitor ◽

Pancreatic Beta Cell ◽

Beta Cell Proliferation ◽

Inhibitor Protein

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Role of the Interaction Between Nck1 and PERK in Pancreatic Beta Cell Function and Survival

Canadian Journal of Diabetes ◽

10.1016/j.jcjd.2021.09.103 ◽

2021 ◽

Vol 45 (7) ◽

pp. S34

Author(s):

Laure Monteillet ◽

Émilie Courty ◽

Nathalie Jouvet ◽

Marco Gasparrini ◽

Cindy Baldwin ◽

...

Keyword(s):

Beta Cell ◽

Beta Cell Function ◽

Cell Function ◽

Pancreatic Beta Cell ◽

Pancreatic Beta Cell Function

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THE ROLE OF SURVIVIN AND RAF-1 KINASE AGAINST ENHANCEMENT OF PANCREATIC BETA-CELL APOPTOSIS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i11.27671 ◽

2018 ◽

Vol 11 (11) ◽

pp. 344

Author(s):

Eva Decroli ◽

Asman Manaf ◽

Syafril Syahbuddin ◽

Sarwono Waspadji ◽

Dwisari Dillasamola

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Beta Cell ◽

Cell Apoptosis ◽

Pancreatic Beta Cell ◽

Enzyme Linked Immunosorbent Assay ◽

Beta Cell Apoptosis

Objective: This study aimed to reveal differences in levels of survivin and Raf-1 kinase in prediabetes, controlled Type 2 diabetes mellitus (T2DM), uncontrolled T2DM, and their relationship with hemoglobin A1c (HbA1c) levels and serum triglyceride levels.Methods: This study was an observational study with a cross-sectional design. The study involved 60 people with T2DM who visited the endocrine and metabolic clinic and 30 prediabetes patients. The variables were survivin levels and Raf-1 kinase enzymes that examined using enzyme-linked immunosorbent assay techniques. HbA1c values are measured by high-performance liquid chromatography and triglyceride levels measured by enzymatic method.Results: Average levels of Raf-1 kinase were significantly higher in the prediabetes group, controlled T2DM, and uncontrolled T2DM (11.6±1.4 pg mL, 9.9±1.1 pg/mL, and 9.1±1.5 pg/mL). Survivin was significantly higher in the prediabetes group, controlled T2DM, and uncontrolled T2DM (5.4±0.4 pg mL, 5.0±0.2 pg/mL, and 4.7±0.1 pg/mL). There was no correlation between HbA1c with Raf-1 kinase levels (R=−0.215, p=0.250), but there was a correlation between HbA1c with serum survivin levels (R=−0.6, *p<0.05). There was a correlation between the levels of triglycerides with survivin but not with Raf-1 kinase (R=−0.267, *p=0.039).Conclusion: Survivin and Raf-1 kinase levels are lower in uncontrolled T2DM. This explained the role of survivin and Raf-1 kinase against enhancement of pancreatic beta-cell apoptosis in patients with T2DM.

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