Objective: To study the comparative importance of environment and genes in the development of islet cell autoimmunity associated with insulin dependent diabetes mellitus.

Design: Population based study of diabetic twins.

Setting: Danish population.

Subjects: 18 monozygotic and 36 dizygotic twin pairs with one or both partners having insulin dependent diabetes.

Main Outcome Measures: Presence of islet cell antibodies, insulin autoantibodies, and autoantibodies to glutamic acid decarboxylase (GAD65) in serum samples from twin pairs 10 years (range 0-30 years) and 9.5 years (2-30 years) after onset of disease.

Results: In those with diabetes the prevalence of islet cell antibodies, insulin autoantibodies, and autoantibodies to glutamic acid decarboxylase in the 26 monozygotic twins was 38%, 85%, and 92%, respectively, and in the dizygotic twins was 57%, 70%, and 57%, respectively. In those without diabetes the proportions were 20%, 50%, and 40% in the 10 monozygotic twins and 26%, 49%, and 40% in the 35 dizygotic twins.

Conclusion: There is no difference between the prevalence of islet cell autoantibodies in dizygotic and monozygotic twins without diabetes, suggesting that islet cell autoimmunity is environmentally rather than genetically determined. Furthermore, the prevalence of islet cell antibodies was higher in the non-diabetic twins than in other first degree relatives of patients with insulin dependent diabetes. This implies that the prenatal or early postnatal period during which twins are exposed to the same environment, in contrast with that experienced by first degree relatives, is of aetiological importance.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2126804PMC
http://dx.doi.org/10.1136/bmj.314.7094.1575DOI Listing

Publication Analysis

Top Keywords

islet cell
28
prevalence islet
16
insulin dependent
16
twin pairs
12
dependent diabetes
12
cell antibodies
12
monozygotic twins
12
population based
8
based study
8
cell autoantibodies
8

Similar Publications

The neuropeptide oxytocin (OXT) and its receptor (OXTR) have been shown to play an important role in glucose metabolism, and pancreatic islets express this ligand and receptor. In the current study, OXTR expression was identified in α-, β-, and δ-cells of the pancreatic islet by RNA hybridization, and OXT protein expression was observed only in β-cells. In order to examine the contribution of islet OXT/OXTR in glycemic control and islet β-cell heath, we developed a β-cell specific OXTR knock-out (β-KO) mouse.

View Article and Find Full Text PDF

β-cell dysfunction in pancreatic islets, characterized as either the loss of β-cell mass or the resistance of β-cell to glucose, is the leading cause of progression to diabetes. Islet transplantation became a promising approach to replenish functional β-cell mass. However, not much known about changes in islets used for transplantation after isolation.

View Article and Find Full Text PDF

During type 1 diabetes (T1D) progression, beta cells become dysfunctional and exhibit reduced first-phase insulin release. While this period of beta cell dysfunction is well established, its cause and underlying mechanism remain unknown. To address this knowledge gap, live human pancreas tissue slices were prepared from autoantibody- negative organ donors without diabetes (ND), donors positive for one or more islet autoantibodies (AAb+), and donors with T1D within 0-4 years of diagnosis (T1D+).

View Article and Find Full Text PDF

Diabetes is associated with the dysfunction of glucagon-producing pancreatic islet α-cells, although the underlying mechanisms regulating glucagon secretion and α-cell dysfunction remain unclear. While insulin secretion from pancreatic β-cells has long been known to be partly controlled by intracellular phospholipid signaling, very little is known about the role of phospholipids in glucagon secretion. Here we show that TMEM55A, a lipid phosphatase that dephosphorylates phosphatidylinositol-4,5-bisphosphate (PIP2) to phosphatidylinositol-5-phosphate (PI5P), regulates α-cell exocytosis and glucagon secretion.

View Article and Find Full Text PDF

Human endocrine cell differentiation and islet morphogenesis play critical roles in determining islet cell mass and function, but the events and timeline of these processes are incompletely defined. To better understand early human islet cell development and maturation, we collected 115 pediatric pancreata and mapped morphological and spatiotemporal changes from birth through the first ten years of life. Using quantitative analyses and a combination of complementary tissue imaging approaches, including confocal microscopy and whole-slide imaging, we developed an integrated model for endocrine cell formation and islet architecture, including endocrine cell type heterogeneity and abundance, endocrine cell proliferation, and islet vascularization and innervation.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!