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A newly discovered role of transcription factors involved in pancreas development and the pathogenesis of diabetes mellitus

, : A newly discovered role of transcription factors involved in pancreas development and the pathogenesis of diabetes mellitus. Proceedings of the Association of American Physicians 110(1): 12-21

The prevalence of diabetes mellitus is increasing worldwide, averaging 5% to 15% in various population groups. Diabetes predisposes to premature morbidity and death. The underlying metabolic cause of diabetes is a failure of the beta-cells of the pancreas to provide insulin in amounts sufficient to meet the body's needs, leading to hyperglycemia. Juvenile (type 1) diabetes results from immune destruction of the beta-cells. Adult onset (type 2) diabetes, which accounts for 90% of all forms of diabetes, is a complex polygenic disease manifested in a dysregulation of insulin secretion. Environmental influences and complex genetic traits contribute to the pathogenesis of both types of diabetes. However, a subpopulation of type 2 diabetes is monogenic and due to inactivating mutations in genes that are critical for normal beta-cell function. Heterozygous carriers of the mutant genes develop early-onset diabetes known as MODY (mature onset diabetes of the young). Notably, three MODY genes encode transcription factors implicated in the regulation of insulin gene transcription: hepatocyte nuclear factors 1 alpha and 4 alpha, and islet duodenum homeobox-1 (IDX-1, also known as IPF-1). The fourth gene encodes glucokinase, the rate-limiting enzyme required for glucose metabolism in beta-cells. Further, an individual born without a pancreas (agenesis) is homozygous for an inactivating mutation of the IDX-1 gene, recapitulating the phenotype of the IDX-1 knockout mouse and demonstrating that expression of IDX-1 is critical for pancreas development. Recently, mouse knockouts of the transcription factors Pax4, Pax6, beta 2/neuroD, and Isl-1 result in severe anomalies in the development of the endocrine pancreas. Gene mutations for these factors are possible candidates for additional MODY genes.


PMID: 9460079

Other references

Nyland, J.A.; Caborn, D.N.M.; Johnson, D.L.; Shapiro, R., 1998: Hamstring fatigue during crossover cutting causes dynamic knee control deficits. Medicine & Science in Sports & Exercise 30(5 SUPPL ): S48, May

Umeda, K.; Saito, K.; Shintani, Y.; Okamoto, J.; Matsumoto, S.; Arimori, M.; Ebine, S.; Maruyama, M.; Kumakura, K.; Kubota, H., 1976: Dietary preparation for direct air-contrast colon examination. Rinsho Hoshasen. Clinical Radiography 21(3 Suppl): 293-298

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Hafiez, A.A.; Abdel-Hafez, M.A.; Salem, D.; Abdou, M.A.; Helaly, A.A.; Aarag, A.H., 1990: Calcium homeostasis in untreated pulmonary tuberculosis. I--Basic study. This study has been done to evaluate serum calcium, phosphorus (P), magnesium, parathyroid hormone (PTH), calcitonin (CT), and cyclic adenosine monophosphate (cAMP) in recently diagnosed pulmonary tuberculous patient, (n = 61) and the results were...

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