Mutational analysis of the coding regions of the genes encoding protein kinase B-α and -β, phosphoinositide-dependent protein kinase-1, phosphatase targeting to glycogen, protein phosphatase inhibitor-1, and glycogenin

Lessons from a search for genetic variability of the insulin-stimulated glycogen synthesis pathway of skeletal muscle in NIDDM patients

Lars Hansen, Helle Fjordvang, Søren K. Rasmussen, Henrik Vestergaard, Søren M. Echwald, Torben Hansen, Dario Alessi, Shirish Shenolikar, Alan R. Saltiel, Fabrizio Barbetti, Oluf Pedersen

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The finding of a reduced insulin-stimulated glucose uptake and glycogen synthesis in the skeletal muscle of glucose-tolerant first-degree relatives of patients with NIDDM, as well as in cultured fibroblasts and skeletal muscle cells isolated from NIDDM patients, has been interpreted as evidence for a genetic involvement in the disease. The mode of inheritance of the common forms of NIDDM is as yet unclear, but the prevailing hypothesis supports a polygenic model. In the present study, we tested the hypothesis that the putative inheritable defects of insulin-stimulated muscle glycogen synthesis might be caused by genetic variability in the genes encoding proteins shown by biochemical evidence to be involved in insulin-stimulated glycogen synthesis in skeletal muscle. In 70 insulin-resistant Danish NIDDM patients, mutational analysis by reverse transcription-polymerase chain reaction-single strand conformation polymorphism-heteroduplex analysis was performed on genomic DNA or skeletal muscle-derived cDNAs encoding glycogenin, protein phosphatase inhibitor-1, phosphatase targeting to glycogen, protein kinase B-α and -β, and the phosphoinositide-dependent protein kinase-1. Although a number of silent variants were identified in some of the examined genes, we found no evidence for the hypothesis that the defective insulin-stimulated glycogen synthesis in skeletal muscle in NIDDM is caused by structural changes in the genes encoding the known components of the insulin-sensitive glycogen synthesis pathway of skeletal muscle.

Original languageEnglish
Pages (from-to)403-407
Number of pages5
JournalDiabetes
Volume48
Issue number2
DOIs
Publication statusPublished - 1999

Fingerprint

Proto-Oncogene Proteins c-akt
Phosphatidylinositols
Glycogen
Phosphoric Monoester Hydrolases
Protein Kinases
Type 2 Diabetes Mellitus
Skeletal Muscle
Insulin
Proteins
Heteroduplex Analysis
Glucose
Muscle Cells
Genes
Reverse Transcription
glycogenin
protein phosphatase inhibitor-1
Complementary DNA
Fibroblasts
Muscles
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Mutational analysis of the coding regions of the genes encoding protein kinase B-α and -β, phosphoinositide-dependent protein kinase-1, phosphatase targeting to glycogen, protein phosphatase inhibitor-1, and glycogenin : Lessons from a search for genetic variability of the insulin-stimulated glycogen synthesis pathway of skeletal muscle in NIDDM patients. / Hansen, Lars; Fjordvang, Helle; Rasmussen, Søren K.; Vestergaard, Henrik; Echwald, Søren M.; Hansen, Torben; Alessi, Dario; Shenolikar, Shirish; Saltiel, Alan R.; Barbetti, Fabrizio; Pedersen, Oluf.

In: Diabetes, Vol. 48, No. 2, 1999, p. 403-407.

Research output: Contribution to journalArticle

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