Insulin biosynthesis and diabetes mellitus

Alan Permutt, John Chirgwin, Steve Giddings, Keiji Kakita, Peter Rotwein

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

This review reports the use of recombinant DNA techniques in the study of the structure and regulation of expression of insulin genes in man and experimental animals. Insulin biosynthesis by pancreatic islet cells is predominantly regulated by change in plasma glucose concentration. Using a cell-free protein synthesizing system as an assay of functional proinsulin messenger RNA (mRNA), and hybridization analysis with a cloned DNA complementary to proinsulin mRNA, it has been determined that at least part of glucose regulation of insulin hiosynthesis occurs through changes in proinsulin mRNA levels. Insulin genes of the rat, chicken and human have been isolated and sequenced. The 5′ ends of the genes have similar sequences suggesting areas important for regulation of transcription. There are two non-allelic insulin genes in the rat, but only one in chickens and humans. Intervening sequences, areas of DNA transcribed into precursor mRNA but which do not appear in mature mRNA, have been described within insulin genes. The insulin gene resides on chromosome 11 of humans as determined by DNA hybridization analysis of mouse human hybrid cells. The structure of the insulin gene in genomic DNA of humans has been analyzed in diabetics and non-diabetics. Insertions of DNA between 1500 and 3400 base pairs have been detected near the transcription initiation site in 65% of type II diabetics, and 25-30% of non-diabetics (this difference is significant at the p

Original languageEnglish (US)
Pages (from-to)230-236
Number of pages7
JournalClinical Biochemistry
Volume14
Issue number5
DOIs
StatePublished - 1981
Externally publishedYes

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Biosynthesis
Medical problems
Diabetes Mellitus
Insulin
Genes
Proinsulin
Messenger RNA
DNA
Islets of Langerhans
Rats
Chickens
Glucose
Chromosomes, Human, Pair 11
Recombinant DNA
Hybrid Cells
Transcription Initiation Site
RNA Precursors
Gene Expression Regulation
Transcription
Chromosomes

ASJC Scopus subject areas

  • Clinical Biochemistry

Cite this

Insulin biosynthesis and diabetes mellitus. / Permutt, Alan; Chirgwin, John; Giddings, Steve; Kakita, Keiji; Rotwein, Peter.

In: Clinical Biochemistry, Vol. 14, No. 5, 1981, p. 230-236.

Research output: Contribution to journalArticle

Permutt, A, Chirgwin, J, Giddings, S, Kakita, K & Rotwein, P 1981, 'Insulin biosynthesis and diabetes mellitus', Clinical Biochemistry, vol. 14, no. 5, pp. 230-236. https://doi.org/10.1016/S0009-9120(81)90940-1
Permutt, Alan ; Chirgwin, John ; Giddings, Steve ; Kakita, Keiji ; Rotwein, Peter. / Insulin biosynthesis and diabetes mellitus. In: Clinical Biochemistry. 1981 ; Vol. 14, No. 5. pp. 230-236.
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