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

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

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

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

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, 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 language	English
Journal	Diabetes
Volume	48
Issue number	2
Pages (from-to)	403-7
Number of pages	5
ISSN	0012-1797
Publication status	Published - Feb 1999

Keywords

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

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Hansen, L., Fjordvang, H., Rasmussen, S. K., Vestergaard, H., Echwald, S. M., Hansen, T., Alessi, D., Shenolikar, S., Saltiel, A. R., Barbetti, F., & Pedersen, O. (1999). 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. Diabetes, 48(2), 403-7.

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. / Hansen, L; Fjordvang, H; Rasmussen, S K et al.
In: Diabetes, Vol. 48, No. 2, 02.1999, p. 403-7.

Research output: Contribution to journal › Journal article › Research › peer-review

Hansen, L, Fjordvang, H, Rasmussen, SK, Vestergaard, H, Echwald, SM, Hansen, T, Alessi, D, Shenolikar, S, Saltiel, AR, Barbetti, F & Pedersen, O 1999, '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', Diabetes, vol. 48, no. 2, pp. 403-7.

Hansen L, Fjordvang H, Rasmussen SK, Vestergaard H, Echwald SM, Hansen T et al. 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. Diabetes. 1999 Feb;48(2):403-7.

Hansen, L ; Fjordvang, H ; Rasmussen, S K et al. / 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. In: Diabetes. 1999 ; Vol. 48, No. 2. pp. 403-7.

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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, 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.",

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author = "L Hansen and H Fjordvang and Rasmussen, {S K} and H Vestergaard and Echwald, {S{\o}ren Morgenthaler} and T Hansen and D Alessi and S Shenolikar and Saltiel, {A R} and F Barbetti and O Pedersen",

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AU - Hansen, L

AU - Fjordvang, H

AU - Rasmussen, S K

AU - Vestergaard, H

AU - Echwald, Søren Morgenthaler

AU - Hansen, T

AU - Alessi, D

AU - Shenolikar, S

AU - Saltiel, A R

AU - Barbetti, F

AU - Pedersen, O

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N2 - 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.

AB - 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.

KW - 3-Phosphoinositide-Dependent Protein Kinases

KW - Carrier Proteins

KW - DNA Mutational Analysis

KW - Diabetes Mellitus, Type 2

KW - Endoribonucleases

KW - Female

KW - Genetic Variation

KW - Glucosyltransferases

KW - Glycogen

KW - Glycoproteins

KW - Humans

KW - Insulin

KW - Intracellular Signaling Peptides and Proteins

KW - Isomerism

KW - Male

KW - Middle Aged

KW - Muscle, Skeletal

KW - Phenotype

KW - Phosphoprotein Phosphatases

KW - Protein-Serine-Threonine Kinases

KW - Proto-Oncogene Proteins

KW - Proto-Oncogene Proteins c-akt

KW - RNA-Binding Proteins

M3 - Journal article

C2 - 10334321

SN - 0012-1797

VL - 48

SP - 403

EP - 407

JO - Diabetes

JF - Diabetes

IS - 2

ER -