Gluco-lipotoxicity of the pancreatic beta cell

doi:10.1016/S0003-4266(04)95628-4

Annales d'Endocrinologie

Volume 65, Issue 1, February 2004, Pages 37-41

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Références (42)

S. Basu et al.
“BAD enables ceramide to signal apoptosis via Ras and Raf-1 ”
J Biol Chem
(1998)
B.E. Corkey et al.
“A role for malonyl Co A in glucose-stimulated insulin secretion from clonal pancreatic beta-cells ”
J Biol Chem
(1989)
S. Gremlich et al.
“Fatty acids decrease IDX-1 expression in rat pancreatic islets and reduce GLUT2, glucokinase, insulin, and somatostatin levels. ”
J Biol Chem
(1997)
S. Jacqueminet et al.
“Inhibition of insulin gene expression by long-term exposure of pancreatic beta-cells to palmitate is dependent upon the presence of a stimulatory glucose concentration. ”
Metabolism
(2000)
C.L. Kelpe et al.
“Palmitate inhibition of insulin gene expression is mediated at the transcriptional level via ceramide synthesis. ”
J Biol Chem
(2003)
A.V. Medvedev et al.
“Regulation of the uncoupling protein-2 gene in INS-1 beta-cells by oleic acid. ”
J Biol Chem
(2002)
M. Prentki et al.
“Malonyl-Co A and long chain acyl-Co A esters as metabolic coupling factors in nutrient-induced insulin secretion. ”
J Biol Chem
(1992)
R. Roduit et al.
“Glucose Down-regulates the Expression of the Peroxisome Proliferator-activated Receptor-alpha Gene in the Pancreatic beta -Cell. ”
J Biol Chem
(2000)
C. Schmitz-Peiffer et al.
“Ceramide generation is sufficient to account for the inhibition of the insulin-stimulated PKB pathway in C2C12 skeletal muscle cells pretreated with palmitate. ”
J Biol Chem
(1999)
M. Shimabukuro et al.
“Lipoapoptosis in beta-cells of obese prediabetic fa/fa rats. Role of serine palmitoyltransferase overexpression. ”
J Biol Chem
(1998)

C.-Y. Zhang et al.

“Uncoupling protein-2 negatively regulates insulin secretion and is a major link between obesity, beta-cell dysfunction, and Type 2 diabetes. ”

Cell

(2001)

H. Zhou et al.

“Inhibition of Akt kinase by cell-permeable ceramide and its implications for ceramide-induced apoptosis. ”

J Biol Chem

(1998)

“Overview of 6 years’ therapy of type II diabetes: a progressive disease. U. K. Prospective Diabetes Study Group. ”

Diabetes

(1995)

C. Berne

“The metabolism of lipids in mouse pancreatic islets; the biosynthesis of triacylglycerols and phospholipids. ”

Biochem J

(1975)

I. Briaud et al.

“Lipotoxicity of the pancreatic beta-cell is associated with glucose-dependent esterification of fatty acids into neutral lipids ”

Diabetes

(2001)

I. Briaud et al.

“Differential effects of hyperlipidemia on insulin secretion in islets of Langerhans from hyperglycemic vs. normoglycemic rats ”

Diabetes

(2002)

G. Silva Xavier et al.

“Role of AMP-activated protein kinase in the regulation by glucose of islet beta cell gene expression. ”

Proc Natl Acad Sci U S A

(2000)

R.A. De Fronzo

“Pathogenesis of type 2 diabetes: metabolic and molecular implications for identifying diabetes genes. ”

Diabetes Reviews

(1999)

R.L. Dobbins et al.

“Circulating fatty acids are essential for efficient glucose-stimulated insulin secretion after prolonged fasting in humans”

Diabetes

(1998)

W. El-Assaad et al.

“Saturated fatty acids synergize with elevated glucose to cause pancreatic beta-cell death.s ”

Endocrinology

(2003)

Farfari S, Schulz V, Corkey B, Prentki M. “Glucose-regulated anaplerosis and cataplerosis in pancreatic...

Cited by (16)

The clinical and metabolic characteristics of young-onset ketosis-prone type 2 diabetes in China
2015, Endocrine Practice
Citation Excerpt :
Our data support the hypothesis that a disturbance in glucose metabolism might play an important role in the pathogenesis of KPD. Some studies have proven that β- and α-cell dysfunction both contribute to the pathophysiology of KPD (31), but the role of lipotoxicity in the β-cell failure observed in KPD patients is controversial (32–34). In our study, the lipid profile was more severely disturbed in the KPD group than in the type 1 diabetes or type 2 diabetes groups.
Objective: To investigate the prevalence and clinical characteristics of ketosis-prone type 2 diabetes (KPD) in Chinese patients with young-onset diabetes.
Methods: A total of 238 young diabetic patients were recruited from our inpatient department from January 1, 2012, to December 28, 2014. KPD was defined as diabetes without precipitating illness and with the presence of ketosis or diabetic ketoacidosis in the absence of autoantibodies at the time of diagnosis. We reviewed the clinical characteristics and disease progression of this group of patients.
Results: Eighteen patients fulfilled the criteria for KPD, and the prevalence of patients with KPD was 7.6%. The mean (SD) age of the KPD group at the time of diagnosis of diabetes was 27.6 (4.85) years, and these patients were predominantly male (male to female ratio, 8:1) and had a high proportion of obesity and new-onset diabetes and a strong family history of diabetes. β-Cell function in the KPD group was intermediate between type 1 and type 2 diabetes. Patients with KPD had the highest levels of glycated hemoglobin, triglycerides, total cholesterol, and free fatty acids and the lowest levels of high-density lipoprotein. After 3 to 12 months of follow-up, 17 of 18 patients with KPD (94.4%) were able to discontinue insulin therapy, and 11 patients (61.1%) were managed with diet or exercise alone.
Conclusion: KPD patients accounted for 7.6% of the diabetic patients requiring admission to a large urban hospital in China, with an age of onset of diabetes of ≤35 years. These patients are more likely to be male, have abnormal lipid metabolism, and have more reversible β-cell dysfunction.
Abbreviations:
BMI = body mass index
DKA = diabetic ketoacidosis
GAD 65 = glutamate decarboxylase 65
HbA _1c = glycated hemoglobin
ICAs = islet-cell antibodies
KPD = ketosis-prone type 2 diabetes mellitus
LADA = latent autoimmune diabetes in an adult
MIDD = maternally inherited diabetes and deafness
MODY = maturityonset diabetes of the young
T1DM = type 1 diabetes mellitus
T2DM = type 2 diabetes mellitus
New avenues for the pharmacological management of type 2 diabetes: An update
2012, Annales d'Endocrinologie
Citation Excerpt :
Similar to the action of incretins, circulating free fatty acids (FFA) play a critical role on pancreatic β-cell physiology, especially on insulin secretion [66,67]. The chronic increase of FFA a phenomenon called lipotoxicity, has been well described to be a major player in the pathophysiology of T2DM, at least by inhibiting insulin secretion and leading to β-cell apoptosis [68]. Conversely, circulating FFA are also able to amplify early insulin secretion, as physiologically observed during food intake [69].
Type 2 diabetes mellitus (T2DM) is one of the most troubling chronic disease regarding the huge number of new cases diagnosed annually worldwide. Currently available oral antidiabetic drugs (OADs) attempt to correct the underlying pathophysiological dysfunctions leading to T2DM: insulin resistance for the insulin sensitizers (metformin and thiazolidinediones), and impaired insulin secretion for the insulin secretagogues (sulfonylureas, glinides and more recently incretin mimetics). Incretin-based therapies include GLP-1 receptor agonists that provide pharmacologic levels of GLP-1 receptor stimulation beyond those that would occur from the action of the native hormone alone, and dipeptidyl-peptidase-4 (DPP-4) inhibitors that preserve endogenous GLP-1 by decreasing its degradation by the DPP-4 enzyme. In 2012, the development of new OADs aims to target untapped pathophysiological aspects of the disease (kidney homeostasis, glucagon signalling, chronic low-grade inflammation) for tailoring glycaemic control in T2DM. SGLT-2 inhibitors are the most advanced new OADs that lower HbA1C by increasing glycosuria and lead to a moderate weight loss. Although there is genuine hope that the range of OADs can be extended, a long-term evaluation of side effects and true clinical benefits is necessary.
Le diabète de type 2 (DT2) représente l’une des maladies chroniques les plus préoccupantes, en regard du nombre exponentiel de nouveaux cas diagnostiqués chaque année dans le monde. Les thérapies hypoglycémiantes orales actuellement disponibles tentent de corriger les dysfonctionnements métaboliques qui caractérisent la maladie : « insulinorésistance », pour les traitements insulinosensibilisateurs (metformine et glitazones), et « insulinopénie relative » pour les traitements insulinosécrétagogues tels que les sulfamides hypoglycémiants, les glinides, et plus récemment les incrétinomimétiques. Ces derniers comprennent les agonistes du récepteur aux GLP-1 qui permettent d’obtenir des taux pharmacologiques supérieurs à ceux du GLP-1 endogène seul pour stimuler son récepteur spécifique, et les inhibiteurs de la dipeptidyl-peptidase 4 (DPP-4) qui s’opposent à la dégradation du GLP-1 endogène habituellement médiée par cette enzyme. En 2012, les traitements hypoglycémiants en cours d’évaluation dans le DT2 ciblent de nouveaux axes physiopathologiques jusqu’alors inexploités (homéostasie glucidique rénale, signalisation du glucagon, inflammation chronique) afin d’optimiser le contrôle glycémique, Les inhibiteurs de SGLT2 représentent, à ce stade, les molécules les plus avancées dans leur développement. Bien que l’éventail de ces nouvelles molécules soit large, une évaluation sur le long terme des effets indésirables et du réel bénéfice clinique est nécessaire.
The metabolic syndrome. Beyond the insulin resistance syndrome
2006, Pharmacological Research
The first series of cases of ketosisprone type 2 diabetes (Flatbush diabetes) in Brazilian adults
2021, Archives of Endocrinology and Metabolism
Mechanism of Pentagalloyl Glucose in Alleviating Fat Accumulation in Caenorhabditis elegans
2019, Journal of Agricultural and Food Chemistry
Antioxidative property and molecular mechanisms underlying geniposide-mediated therapeutic effects in diabetes mellitus and cardiovascular disease
2019, Oxidative Medicine and Cellular Longevity

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Session 1Gluco-lipotoxicity of the pancreatic beta cell

First page preview

J Biol Chem

J Biol Chem

J Biol Chem

Metabolism

J Biol Chem

J Biol Chem

J Biol Chem

J Biol Chem

J Biol Chem

J Biol Chem

Cell

J Biol Chem

“Overview of 6 years’ therapy of type II diabetes: a progressive disease. U. K. Prospective Diabetes Study Group. ”

Diabetes

“The metabolism of lipids in mouse pancreatic islets; the biosynthesis of triacylglycerols and phospholipids. ”

Biochem J

“Lipotoxicity of the pancreatic beta-cell is associated with glucose-dependent esterification of fatty acids into neutral lipids ”

Diabetes

“Differential effects of hyperlipidemia on insulin secretion in islets of Langerhans from hyperglycemic vs. normoglycemic rats ”

Diabetes

“Role of AMP-activated protein kinase in the regulation by glucose of islet beta cell gene expression. ”

Proc Natl Acad Sci U S A

“Pathogenesis of type 2 diabetes: metabolic and molecular implications for identifying diabetes genes. ”

Diabetes Reviews

“Circulating fatty acids are essential for efficient glucose-stimulated insulin secretion after prolonged fasting in humans”

Diabetes

“Saturated fatty acids synergize with elevated glucose to cause pancreatic beta-cell death.s ”

Endocrinology

Session 1
Gluco-lipotoxicity of the pancreatic beta cell