Mutational analysis of the coding regions of the genes encoding protein kinase B-alpha and -beta, 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

Research output: Contribution to journalJournal articleResearchpeer-review

L Hansen, H Fjordvang, S K Rasmussen, H Vestergaard, Søren Morgenthaler Echwald, T Hansen, D Alessi, S Shenolikar, A R Saltiel, F Barbetti, O Pedersen

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, phophatase targeting to glycogen, protein kinase B-alpha and -beta, 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
JournalDiabetes
Volume48
Issue number2
Pages (from-to)403-7
Number of pages5
ISSN0012-1797
Publication statusPublished - Feb 1999

    Research areas

  • 3-Phosphoinositide-Dependent Protein Kinases, Carrier Proteins, DNA Mutational Analysis, Diabetes Mellitus, Type 2, Endoribonucleases, Female, Genetic Variation, Glucosyltransferases, Glycogen, Glycoproteins, Humans, Insulin, Intracellular Signaling Peptides and Proteins, Isomerism, Male, Middle Aged, Muscle, Skeletal, Phenotype, Phosphoprotein Phosphatases, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-akt, RNA-Binding Proteins

ID: 92192413