scholarly journals Lamin C Counteracts Glucose Intolerance in Aging, Obesity, and Diabetes Through β-Cell Adaptation

Diabetes ◽  
2020 ◽  
Vol 69 (4) ◽  
pp. 647-660 ◽  
Author(s):  
Marion de Toledo ◽  
Isabel C. Lopez-Mejia ◽  
Patricia Cavelier ◽  
Marine Pratlong ◽  
Célia Barrachina ◽  
...  
Keyword(s):  
Glucose Intolerance ◽  
Β Cell ◽  
Cell Adaptation ◽  
Obesity And Diabetes

scholarly journals β-cell adaptation in a mouse model of glucocorticoid-induced metabolic syndrome

2013 ◽  
Vol 219 (3) ◽  
pp. 231-241 ◽  
Author(s):  
Liselotte Fransson ◽  
Stephanie Franzén ◽  
Victoria Rosengren ◽  
Petra Wolbert ◽  
Åke Sjöholm ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Drinking Water ◽  
Mouse Model ◽  
Glucose Intolerance ◽  
Body Weight Gain ◽  
Β Cell ◽  
Cell Adaptation ◽  
The Metabolic Syndrome ◽  
Islet Volume

Glucocorticoids (GCs) are stress hormones primarily responsible for mobilizing glucose to the circulation. Due to this effect, insulin resistance and glucose intolerance are concerns in patients with endogenous overproduction of GCs and in patients prescribed GC-based therapy. In addition, hypercortisolemic conditions share many characteristics with the metabolic syndrome. This study reports on a thorough characterization, in terms of glucose control and lipid handling, of a mouse model where corticosterone is given via the drinking water. C57BL/6J mice were treated with corticosterone (100 or 25 μg/ml) or vehicle in their drinking water for 5 weeks after which they were subjected to insulin or glucose tolerance tests. GC-treated mice displayed increased food intake, body weight gain, and central fat deposit accumulations. In addition, the GC treatment led to dyslipidemia as well as accumulation of ectopic fat in the liver and skeletal muscle, having a substantial negative effect on insulin sensitivity. Also glucose intolerance and hypertension, both part of the metabolic syndrome, were evident in the GC-treated mice. However, the observed effects of corticosterone were reversed after drug removal. Furthermore, this study reveals insights into β-cell adaptation to the GC-induced insulin resistance. Increased pancreatic islet volume due to cell proliferation, increased insulin secretion capacity, and increased islet chaperone expression were found in GC-treated animals. This model mimics the human metabolic syndrome. It could be a valuable model for studying the complex mechanisms behind the development of the metabolic syndrome and type 2 diabetes, as well as the multifaceted relations between GC excess and disease.

scholarly journals Vitamin B6 deficiency disrupts serotonin signaling in pancreatic islets and induces gestational diabetes in mice

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Ashley M. Fields ◽  
Kevin Welle ◽  
Elaine S. Ho ◽  
Clementina Mesaros ◽  
Martha Susiarjo
Keyword(s):  
Cell Proliferation ◽  
Insulin Secretion ◽  
Pancreatic Islets ◽  
Glucose Intolerance ◽  
Vitamin B6 ◽  
Serotonin Receptor ◽  
Dependent Manner ◽  
Β Cell ◽  
Vitamin B6 Deficiency ◽  
Maternal Glucose

AbstractIn pancreatic islets, catabolism of tryptophan into serotonin and serotonin receptor 2B (HTR2B) activation is crucial for β-cell proliferation and maternal glucose regulation during pregnancy. Factors that reduce serotonin synthesis and perturb HTR2B signaling are associated with decreased β-cell number, impaired insulin secretion, and gestational glucose intolerance in mice. Albeit the tryptophan-serotonin pathway is dependent on vitamin B6 bioavailability, how vitamin B6 deficiency impacts β-cell proliferation during pregnancy has not been investigated. In this study, we created a vitamin B6 deficient mouse model and investigated how gestational deficiency influences maternal glucose tolerance. Our studies show that gestational vitamin B6 deficiency decreases serotonin levels in maternal pancreatic islets and reduces β-cell proliferation in an HTR2B-dependent manner. These changes were associated with glucose intolerance and insulin resistance, however insulin secretion remained intact. Our findings suggest that vitamin B6 deficiency-induced gestational glucose intolerance involves additional mechanisms that are complex and insulin independent.

scholarly journals Disruption of the Dopamine D2 Receptor Impairs Insulin Secretion and Causes Glucose Intolerance

Endocrinology ◽  
2010 ◽  
Vol 151 (4) ◽  
pp. 1441-1450 ◽  
Author(s):  
Isabel García-Tornadú ◽  
Ana M. Ornstein ◽  
Astrid Chamson-Reig ◽  
Michael B. Wheeler ◽  
David J. Hill ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Glucose Intolerance ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Insulin Response ◽  
Wild Type ◽  
Β Cell ◽  
Insulin Response To Glucose

The relationship between antidopaminergic drugs and glucose has not been extensively studied, even though chronic neuroleptic treatment causes hyperinsulinemia in normal subjects or is associated with diabetes in psychiatric patients. We sought to evaluate dopamine D2 receptor (D2R) participation in pancreatic function. Glucose homeostasis was studied in D2R knockout mice (Drd2−/−) mice and in isolated islets from wild-type and Drd2−/− mice, using different pharmacological tools. Pancreas immunohistochemistry was performed. Drd2−/− male mice exhibited an impairment of insulin response to glucose and high fasting glucose levels and were glucose intolerant. Glucose intolerance resulted from a blunted insulin secretory response, rather than insulin resistance, as shown by glucose-stimulated insulin secretion tests (GSIS) in vivo and in vitro and by a conserved insulin tolerance test in vivo. On the other hand, short-term treatment with cabergoline, a dopamine agonist, resulted in glucose intolerance and decreased insulin response to glucose in wild-type but not in Drd2−/− mice; this effect was partially prevented by haloperidol, a D2R antagonist. In vitro results indicated that GSIS was impaired in islets from Drd2−/− mice and that only in wild-type islets did dopamine inhibit GSIS, an effect that was blocked by a D2R but not a D1R antagonist. Finally, immunohistochemistry showed a diminished pancreatic β-cell mass in Drd2−/− mice and decreased β-cell replication in 2-month-old Drd2−/− mice. Pancreatic D2Rs inhibit glucose-stimulated insulin release. Lack of dopaminergic inhibition throughout development may exert a gradual deteriorating effect on insulin homeostasis, so that eventually glucose intolerance develops.

scholarly journals Protein-conformational diseases in childhood: Naturally-occurring hIAPP amyloid-oligomers and early β-cell damage in obesity and diabetes

PLoS ONE ◽  
2020 ◽  
Vol 15 (8) ◽  
pp. e0237667
Author(s):  
Nelly F. Altamirano-Bustamante ◽  
Eulalia Garrido-Magaña ◽  
Eugenia Morán ◽  
Aurora Calderón ◽  
Karina Pasten-Hidalgo ◽  
...  
Keyword(s):  
Cell Damage ◽  
Β Cell ◽  
Conformational Diseases ◽  
Naturally Occurring ◽  
Obesity And Diabetes ◽  
Amyloid Oligomers

β-Cell Glucose Non-sensing in Patients with Thalassemia major and Glucose Intolerance

1995 ◽  
pp. 157-160
Author(s):  
G. Petrou ◽  
M. Makri ◽  
A. Armoni ◽  
B. E. Spiliotis ◽  
T. K. Alexandrides
Keyword(s):  
Glucose Intolerance ◽  
Thalassemia Major ◽  
Β Cell ◽  
Cell Glucose

scholarly journals Alpha1-antitrypsin ameliorates islet amyloid-induced glucose intolerance and β-cell dysfunction

2020 ◽  
Vol 37 ◽  
pp. 100984
Author(s):  
Júlia Rodríguez-Comas ◽  
Juan Moreno-Vedia ◽  
Mercè Obach ◽  
Carlos Castaño ◽  
Sara de Pablo ◽  
...  
Keyword(s):  
Glucose Intolerance ◽  
Β Cell ◽  
Islet Amyloid ◽  
Cell Dysfunction ◽  
Alpha1 Antitrypsin

scholarly journals Epigenetics in β-cell adaptation and type 2 diabetes

2020 ◽  
Vol 55 ◽  
pp. 125-131
Author(s):  
Hyunki Kim ◽  
Rohit N. Kulkarni
Keyword(s):  
Type 2 Diabetes ◽  
Β Cell ◽  
Cell Adaptation

scholarly journals Reduction of islet pyruvate carboxylase activity might be related to the development of type 2 diabetes mellitus in Agouti-K mice

2009 ◽  
Vol 204 (2) ◽  
pp. 143-152 ◽  
Author(s):  
J Han ◽  
Y Q Liu
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Blood Glucose ◽  
Protein Level ◽  
Pyruvate Carboxylase ◽  
Β Cell ◽  
Cell Adaptation ◽  
Type 2 Diabetic

Pyruvate carboxylase (PC) activity is enhanced in the islets of obese rats, but it is reduced in the islets of type 2 diabetic rats, suggesting the importance of PC in β-cell adaptation to insulin resistance as well as the possibility that PC reduction might lead to hyperglycemia. However, the causality is currently unknown. We used obese Agouti mice (AyL) as a model to show enhanced β-cell adaptation, and type 2 diabetic db/db mice as a model to show severe β-cell failure. After comparison of the two models, a less severe type 2 diabetic Agouti-K (AyK) mouse model was used to show the changes in islet PC activity during the development of type 2 diabetes mellitus (T2DM). AyK mice were separated into two groups: mildly (AyK-M, blood glucose <250 mg/dl) and severely (AyK-S, blood glucose >250 mg/dl) hyperglycemic. Islet PC activity, but not protein level, was increased 1.7-fold in AyK-M mice; in AyK-S mice, islet PC activity and protein level were reduced. All other changes including insulin secretion and islet morphology in AyK-M mice were similar to those observed in AyL mice, but they were worse in AyK-S mice where these parameters closely matched those in db/db mice. In 2-day treated islets, PC activity was inhibited by high glucose but not by palmitate. Our findings suggest that islet PC might play a role in the development of T2DM where reduction of PC activity might be a consequence of mild hyperglycemia and a cause for severe hyperglycemia.

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