The pancreatic islets in diabetes

Gepts, W; LeCompte, Philip M.

doi:10.1016/0002-9343(81)90417-4

Cited by 320 publications

(176 citation statements)

References 62 publications

Supporting

Mentioning

160

Contrasting

Unclassified

Order By: Relevance

“…The histopathological hallmarks of the disease comprise a markedly reduced ␤-cell mass and a focal infiltration of the islets by mononuclear cells termed insulitis (2). Very little is known about the nature, intensity, and kinetics of the underlying histopathological lesions during the allegedly long preclinical disease phase (3,4).…”

Section: Diabetes Care 23:1072-1078 2000mentioning

confidence: 99%

Use of an islet cell antibody assay to identify type 1 diabetic patients with rapid decrease in C-peptide levels after clinical onset. Belgian Diabetes Registry.

Decochez

Keymeulen²,

Somers³

et al. 2000

Diabetes Care

View full text Add to dashboard Cite

OBJECTIVE -To investigate whether the presence of antibody markers at diagnosis could help predict the rapid decrease in residual ␤-cell function noted in some, but not all, patients with recent-onset type 1 diabetes.RESEARCH DESIGN AND METHODS -We measured random C-peptide levels (radioimmunoassay); islet cell cytoplasmic antibodies (ICA) (indirect immunofluorescence); and antibodies against IA-2 protein, 65-kDa glutamate decarboxylase, and insulin (liquid-phase radiobinding assays) in 172 patients Ͻ40 years of age with type 1 diabetes. The patients had been consecutively recruited at diagnosis by the Belgian Diabetes Registry and were followed for 2 years.RESULTS -Two years after diagnosis, random C-peptide levels had decreased significantly (P Ͻ 0.001) in ICA ϩ patients but not in ICA Ϫ patients. C-peptide values Ͻ50 pmol/l were noted in 88% of patients diagnosed before 7 years of age, in 45% of patients diagnosed between ages 7 and 15 years, and in 29% of patients diagnosed after 15 years of age (P Ͻ 0.001). In cases of clinical onset before age 15 years, a rapid decline in random C-peptide values was observed almost exclusively in patients with high-titer ICA (Ն50 Juvenile Diabetes Foundation [JDF] units) at diagnosis (69 vs. 17% in patients with lower ICA titers, P Ͻ 0.001). In patients diagnosed after 15 years of age, 36% of patients with ICA titers Ն12 JDF units developed low C-peptide levels compared with 14% of patients with ICA titers Ͻ12 JDF units (P Ͻ 0.03). Multivariate analysis confirmed that C-peptide levels after 2 years were inversely correlated with ICA levels (P Ͻ 0.001) and to a lesser degree positively correlated with age at diagnosis (P Ͻ 0.02), regardless of the levels or number of molecular autoantibodies.CONCLUSIONS -Young age at diagnosis and high-titer ICA identify a group of type 1 diabetic patients at high risk of rapidly losing residual ␤-cell function. Using these selection criteria, it is possible to better target ␤-cell-preserving interventions to patients with or without such rapid progression, depending on the nature of the tested substance. The

show abstract

Section: Diabetes Care 23:1072-1078 2000mentioning

confidence: 99%

Use of an islet cell antibody assay to identify type 1 diabetic patients with rapid decrease in C-peptide levels after clinical onset. Belgian Diabetes Registry.

Decochez

Keymeulen²,

Somers³

et al. 2000

Diabetes Care

View full text Add to dashboard Cite

show abstract

“…In noninsulin-dependent diabetes mellitus the deficit of insulin production is less well characterized. Reductions of B cell number (6,7) and of extractable pancreatic insulin (8,9) have been observed at autopsy, although these findings have not been consistent (3)(4)(5) and their functional significance is unknown. Insulin resistance has been shown to be important in increasing the metabolic demands for insulin, but pathogenetic relationships between insulin sensitivity and capacity to produce insulin remain unclear (10).…”

Section: Introductionmentioning

confidence: 99%

“…Despite an appreciation of the importance of insulin production, there has been no adequate quantitative assessment of capacity to produce insulin in humans. In insulin-dependent diabetes mellitus a deficit in insulin production has been established by the loss of endogenous insulin secretion (1,2), and by a paucity of B cells in pancreas at autopsy (3)(4)(5)(6). In noninsulin-dependent diabetes mellitus the deficit of insulin production is less well characterized.…”

Section: Introductionmentioning

confidence: 99%

Modulation of proinsulin messenger RNA after partial pancreatectomy in rats. Relationships to glucose homeostasis.

Orland¹,

Chyn²,

Permutt³

1985

J. Clin. Invest.

View full text Add to dashboard Cite

These studies of partial pancreatectomy assess pancreatic proinsulin messenger RNA (mRNA) levels as an index of in vivo insulin biosynthesis, and show relationships to glucose homeostasis. Rats were subjected to sham operation, 50% pancreatectomy (Px), or 90% Px, and were examined after 1, 3, or 14 wk. Proinsulin mRNA was measured by dot hybridization to complementary DNA. After 50% Px there was a nearly complete adaptation of proinsulin mRNA. After 90% Px a marked increase of proinsulin mRNA occurred, but it was insufficient and it was not maintained with time. The deficit in insulin production is related to development of hyperglycemia.Sham-operated controls showed no worsening of fasting or fed blood glucose or of intraperitoneal glucose tolerance within the period of observation. Total proinsulin mRNA and pancreatic insulin content rose in proportion to body weight. 50% PN produced no change from controls in body weight or blood glucose. The concentration of proinsulin mRNA in the 50% pancreatic remnant paralleled that of controls after 1 and 3 wk, but then increased after 14 wk, such that total proinsulin mRNA approached control levels. This adaptive response was reflected by changes in serum insulin, but not by pancreatic insulin content, which was only 30% of control after 14 wk. Intraperitoneal glucose tolerance was impaired mildly, and did not worsen with time after pancreatectomy.90% Px led to elevated fed blood glucose and reduced serum insulin after 3 wk, and fasting hyperglycemia was seen after 14 wk. Proinsulin mRNA concentration in the 10% pancreatic remnant showed an adaptive increase after 1 and 3 wk, such that total proinsulin mRNA reached 40% of control. After 14 wk, however, remnant proinsulin mRNA concentration was no longer increased; total proinsulin mRNA and pancreatic insulin content were severely reduced. Intraperitoneal glucose tolerance was impaired more dramatically than with the 50% Px animals, and worsened with time after operation.These observations indicate ability to increase proinsulin mRNA levels as an adaptation to pancreatectomy. Insufficiency of this adaptation is associated with the development of hyperglycemia, and the loss of this adaptation correlates with a worsening of glucose tolerance.

show abstract

“…Recently, it has been shown that exposure to free fatty acids (FFAs) has cytostatic and proapoptotic effects on human pancreatic ␤-cells (6). Furthermore, human autopsy studies show a relative reduction of ␤-cell mass in patients with type 2 diabetes compared with weight-matched nondiabetic subjects (7,8). These findings support the idea that in genetically predisposed human subjects, prolonged exposure to elevated FFAs may contribute to ␤-cell death and development/progression of type 2 diabetes.…”

mentioning

confidence: 99%

Protein Kinase C δ Activation and Translocation to the Nucleus Are Required for Fatty Acid-Induced Apoptosis of Insulin-Secreting Cells

Eitel

Staiger²,

Rieger³

et al. 2003

Diabetes

129

105

View full text Add to dashboard Cite

Insulin resistance as well as pancreatic ␤-cell failure can be induced by elevated free fatty acid (FFA) levels. We studied the mechanisms of FFA-induced apoptosis in rat and human ␤-cells. Chronic treatment with high physiological levels of saturated fatty acids (palmitate and stearate), but not with monounsaturated (palmitoleate and oleate) or polyunsaturated fatty acids (linoleate), triggers apoptosis in ϳ20% of cultured RIN1046-38 cells. Apoptosis restricted to saturated FFAs was also observed in primary cultured human ␤-cells, suggesting that this mechanism is potentially relevant in vivo in humans. To further analyze FFAinduced signaling pathways leading to apoptosis, we used RIN1046-38 cells. Apoptosis was accompanied by a rapid (within 15 min) nuclear translocation of protein kinase C (PKC)-␦ and subsequent lamin B1 disassembly. This translocation was impaired by the phospholipase C inhibitor U-73122, which also substantially reduced apoptosis. Furthermore, lamin B1 disassembly and apoptosis were decreased by cell transfection with a dominant-negative mutant form of PKC-␦. These data suggest that nuclear translocation and kinase activity of PKC-␦ are both necessary for saturated fatty acidinduced apoptosis. Diabetes 52:991-997, 2003

show abstract

The pancreatic islets in diabetes

Cited by 320 publications

References 62 publications

Use of an islet cell antibody assay to identify type 1 diabetic patients with rapid decrease in C-peptide levels after clinical onset. Belgian Diabetes Registry.

Use of an islet cell antibody assay to identify type 1 diabetic patients with rapid decrease in C-peptide levels after clinical onset. Belgian Diabetes Registry.

Modulation of proinsulin messenger RNA after partial pancreatectomy in rats. Relationships to glucose homeostasis.

Protein Kinase C δ Activation and Translocation to the Nucleus Are Required for Fatty Acid-Induced Apoptosis of Insulin-Secreting Cells

Contact Info

Product

Resources

About