Organization of the human carboxypeptidase E gene and molecular scanning for mutations in Japanese subjects with NIDDM or obesity

Diabetologia
N UtsunomiyaK Nanjo

Abstract

Insulin is synthesized in the pancreatic beta cell as a larger precursor molecule proinsulin which is converted to insulin and C-peptide by the concerted action of prohormone convertase 2 (PC2), prohormone convertase 3 (PC3) and carboxypeptidase E (CPE). One of the features of non-insulin-dependent diabetes mellitus (NIDDM) is an elevation in the proinsulin level and/or proinsulin/insulin molar ratio suggesting that mutations in these three proinsulin processing enzymes might contribute to the development of NIDDM. The identification of a mutation in the CPE gene of the fat/fat mouse which leads to marked hyperproinsulinaemia and late-onset obesity and diabetes is consistent with a possible role for mutations in CPE in the development of diabetes and obesity in humans. In order to test this hypothesis, we have isolated and characterized the human CPE gene and screened it for mutations in a group of Japanese subjects with NIDDM and obesity. The human CPE gene consists of 9 exons spanning more than 60 kb. Primer extension analysis identified the transcriptional start site at -141 bp from the translational start site. Single strand conformational polymorphism analysis and nucleotide sequencing of the promoter and entire coding reg...Continue Reading

Citations

Sep 29, 1999·Trends in Biochemical Sciences·L D Fricker, E H Leiter
Oct 19, 2001·Diabetic Medicine : a Journal of the British Diabetic Association·R S Jackson
May 13, 2010·American Journal of Physiology. Endocrinology and Metabolism·Niamh X CawleyY Peng Loh
Mar 10, 2012·Endocrine Reviews·Niamh X CawleyY Peng Loh
Apr 6, 2002·Biological Chemistry·Luciana G PessoaJoão B Pesquero
Jan 29, 2014·Proteomics. Clinical Applications·Matthew R Sapio, Lloyd D Fricker
Aug 1, 2015·Saudi Journal of Gastroenterology : Official Journal of the Saudi Gastroenterology Association·Shu-Long DaiShi-Yong Yang
Jul 20, 2021·Physiological Reviews·Adam Ramzy, Timothy J Kieffer

❮ Previous
Next ❯

Related Concepts

Related Feeds

Biomarkers for Type 2 Diabetes

Biomarkers can help understand chronic diseases and assist in risk prediction for prevention and early detection of diseases. Here is the latest research on biomarkers in type 2 diabetes, a disease in which the body is unable to produce or properly use insulin.