scholarly journals Islet Brain 1 Protects Insulin Producing Cells against Lipotoxicity

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Saška Brajkovic ◽  
Mourad Ferdaoussi ◽  
Valérie Pawlowski ◽  
Hélène Ezanno ◽  
Valérie Plaisance ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Beta Cell ◽  
Cell Survival ◽  
Cell Mass ◽  
Ectopic Expression ◽  
Beta Cell Mass ◽  
Mitogen Activated Protein Kinase ◽  
Interacting Protein ◽  
Mitogen Activated Protein ◽  
And Function

Chronic intake of saturated free fatty acids is associated with diabetes and may contribute to the impairment of functional beta cell mass. Mitogen activated protein kinase 8 interacting protein 1 also called islet brain 1 (IB1) is a candidate gene for diabetes that is required for beta cell survival and glucose-induced insulin secretion (GSIS). In this study we investigated whether IB1 expression is required for preserving beta cell survival and function in response to palmitate. Chronic exposure of MIN6 and isolated rat islets cells to palmitate led to reduction of the IB1 mRNA and protein content. Diminution of IB1 mRNA and protein level relied on the inducible cAMP early repressor activity and proteasome-mediated degradation, respectively. Suppression of IB1 level mimicked the harmful effects of palmitate on the beta cell survival and GSIS. Conversely, ectopic expression of IB1 counteracted the deleterious effects of palmitate on the beta cell survival and insulin secretion. These findings highlight the importance in preserving the IB1 content for protecting beta cell against lipotoxicity in diabetes.

scholarly journals Verapamil can be used as a Type 2 Diabetes Mellitus Saviour and Stopping the need for Insulin in Uncontrolled Type 2 Diabetes Mellitus

2021 ◽  
pp. 1-8
Author(s):  
Mahmoud Younis ◽  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Beta Cell ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Interacting Protein ◽  
Significant Difference ◽  
And Function

Introduction: Diabetes mellitus is not just a disease as it is already known, the matter is more complicated, and it is considered as an assembly of metabolic defects with end result of hyperglycemia.verapamil can decrease the expression of thioredoxin-interacting protein (TXNIP), which is recognized as an important factor in pancreatic beta cells.verapamil could enhance beta cell mass and function. Materials and Methods: 160 type 2 diabetes patients in 2 parallel groups. Results: show statistically significant difference in favour of verapamil in increasing c-peptide levels and decreasing hba1c levels. Conclusion: Verapamil could be used as a type 2 diabetes saviour by increasing beta cell mass and function.

The Effects of Beta-cell Mass and Function, Intercellular Coupling, and islet Synchrony on Ca2+ Dynamics in Patients with Type 2 Diabetes Mellitus

2020 ◽  
Author(s):  
Maryam Saadati ◽  
Yousef Jamali
Keyword(s):  
Insulin Secretion ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
Cell Mass ◽  
Electrical Coupling ◽  
Beta Cell Mass ◽  
Intercellular Coupling ◽  
And Function

Abstract Type 2 diabetes (T2D) is a challenging metabolic disorder characterized by a substantial loss of beta-cell mass via progressive programmed cell death and alteration of beta-cell function in the islets of Langerhans, disrupting insulin secretion and glucose homeostasis. The mechanisms for deficiency in beta-cell mass and function during the hyperglycemia development and T2D pathogenesis are complex. To study the relative contribution of beta-cell mass to beta-cell function in T2D, we make use of a comprehensive electrophysiological model from human beta-cell clusters. We find that defect in beta-cell mass causes a functional decline in single beta-cell, impairment in intra-islet synchrony, and changes in the form of oscillatory patterns of membrane potential and intracellular Ca2+ concentration, which can lead to changes in insulin secretion dynamics and insulin levels. The model demonstrates good correspondence between suppression of synchronizing electrical activity and pulsatile insulin release, and published experimental measurements. We then compare the role of gap junction-mediated electrical coupling with both beta-cell synchronization and metabolic coupling in the behavior of Ca2+ concentration dynamics within human islets. Our results indicate that inter-beta-cellular electrical coupling depicts a more important factor in shaping the physiological regulation of islet function and in human T2D. We further predict that varying the conductance gating of delayed rectifier K+ channels modifies oscillatory activity patterns of the beta-cell population lacking intercellular coupling, which significantly affects Ca2+ concentration and insulin secretion.

2295-PUB: Impaired First-Phase Insulin Secretion Predicts the Development of Hyperglycemia in a Human Model of Acute Beta-Cell Mass Reduction

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 2295-PUB
Author(s):  
TERESA MEZZA ◽  
PIETRO MANUEL FERRARO ◽  
GIANFRANCO DI GIUSEPPE ◽  
CHIARA MARIA ASSUNTA CEFALO ◽  
SIMONA MOFFA ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Beta Cell ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Human Model ◽  
Mass Reduction ◽  
First Phase Insulin Secretion

scholarly journals Disruption of beta cell acetyl-CoA carboxylase-1 in mice impairs insulin secretion and beta cell mass

Diabetologia ◽  
2018 ◽  
Vol 62 (1) ◽  
pp. 99-111 ◽  
Author(s):  
James Cantley ◽  
Aimee Davenport ◽  
Laurène Vetterli ◽  
Nandor J. Nemes ◽  
P. Tess Whitworth ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Beta Cell ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Acetyl Coa Carboxylase ◽  
Acetyl Coa

scholarly journals Effect of Hypertriglyceridemia on Beta Cell Mass and Function in ApoC3 Transgenic Mice

2016 ◽  
Vol 291 (28) ◽  
pp. 14695-14705 ◽  
Author(s):  
Yun-Zi Liu ◽  
Xiaoyun Cheng ◽  
Ting Zhang ◽  
Sojin Lee ◽  
Jun Yamauchi ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Beta Cell ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
And Function

scholarly journals Loss of beta-cell mass leads to a reduction of pulse mass with normal periodicity, regularity and entrainment of pulsatile insulin secretion in G�ttingen minipigs

Diabetologia ◽  
2004 ◽  
Vol 47 (1) ◽  
pp. 155-155
Author(s):  
M. O. Larsen ◽  
C. F. Gotfredsen ◽  
M. Wilken ◽  
R. D. Carr ◽  
N. P�rksen ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Beta Cell ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Pulsatile Insulin Secretion

scholarly journals GK-rats respond to gastric bypass surgery with improved glycemia despite unaffected insulin secretion and beta cell mass

Peptides ◽  
2021 ◽  
Vol 136 ◽  
pp. 170445
Author(s):  
Michael G. Miskelly ◽  
Liliya Shcherbina ◽  
Ann-Helen Thorén Fischer ◽  
Mia Abels ◽  
Andreas Lindqvist ◽  
...  
Keyword(s):  
Gastric Bypass ◽  
Insulin Secretion ◽  
Beta Cell ◽  
Bypass Surgery ◽  
Gastric Bypass Surgery ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Gk Rats

059. POOR GROWTH BEFORE BIRTH IMPAIRS INSULIN SECRETION - WHAT WE HAVE LEARNT ABOUT THE MECHANISMS FROM THE PLACENTALLY-RESTRICTED SHEEP

2009 ◽  
Vol 21 (9) ◽  
pp. 14
Author(s):  
K. L. Gatford
Keyword(s):  
Insulin Resistance ◽  
Insulin Secretion ◽  
Beta Cell ◽  
Insulin Action ◽  
Cell Function ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Poor Growth ◽  
Impaired Insulin ◽  
Impaired Insulin Action

Diabetes occurs when insulin secretion fails to increase sufficiently to compensate for developing insulin resistance. This implies that the increased risk of diabetes in adults who were small at birth reflects impaired insulin secretion as well as their well-known insulin resistance. More recently, direct evidence has been obtained that adults and children who were growth-restricted before birth secrete less insulin than they should, given their level of insulin resistance. Our research group is using the placentally-restricted (PR) sheep to investigate the mechanisms underlying impaired insulin action (sensitivity and secretion) induced by poor growth before birth. Like the intra-uterine growth-restricted (IUGR) human, the PR sheep develops impaired insulin action by adulthood, but has enhanced insulin sensitivity in infancy, associated with neonatal catch-up growth1, 2. Impaired insulin action begins to develop in early postnatal life, where although basal insulin action is high due to enhanced insulin sensitivity, maximal glucose-stimulated insulin action is already impaired in males3. Our cellular and molecular studies have identified impaired beta-cell function rather than mass as the likely cause of impaired insulin secretion, and we have reported a novel molecular defect in the calcium channels involved in the insulin secretion pathway in the pancreas of these lambs3. Upregulation of IGF-II and insulin receptor are implicated as key molecular regulators of beta-cell mass in the PR lamb3. By adulthood, both basal and maximal insulin action are profoundly impaired in the male lamb who was growth-restricted at birth2. These studies suggest therapies to prevent diabetes in the individual who grew poorly before birth should target beta-cell function, possibly in addition to further increasing beta-cell mass, to improve insulin secretion capacity, and its ability to increase in response to development of insulin resistance. We are now using the PR sheep to test potential therapies, since the timing of pancreatic development and hence exposure to a growth-restricting environment, is similar to that of the human.

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