PMID- 10877213 OWN - NLM STAT- MEDLINE DCOM- 20000718 LR - 20131121 IS - 0026-0495 (Print) IS - 0026-0495 (Linking) VI - 49 IP - 6 DP - 2000 Jun TI - Regulation of hexokinase II expression in human skeletal muscle in vivo. PG - 814-8 AB - The phosphorylation of glucose to glucose-6-phosphate (G-6-P) is the first committed step in glucose uptake in skeletal muscle. This reaction is catalyzed by hexokinase (HK). Two HK isoforms, HKI and HKII, are expressed in human skeletal muscle, but only HKII is regulated by insulin. The present study was undertaken to determine the time course for the regulation of HK activity and expression by physiological plasma insulin concentrations in human skeletal muscle in vivo. A hyperinsulinemic-euglycemic glucose clamp and percutaneous muscle biopsy were performed in separate groups of healthy subjects after 60, 120, 180, and 360 minutes of euglycemic hyperinsulinemia. Muscle biopsies were subfractionated into soluble and particulate fractions to determine HKI and HKII activities. RNA was extracted from a separate portion of the muscle biopsy, and HKI and HKII mRNA content was determined using an RNase protection assay. Glycogen synthase (GS) activity and fractional velocity were also determined. HKII mRNA was increased 2-fold by 120 minutes and remained high versus the basal value for up to 360 minutes. HKI mRNA was unchanged throughout the study. HKII activity increased after 360 minutes of insulin infusion, and this increase was limited to the soluble fraction. In contrast, insulin induced a 1.5- to 2-fold increase in GS fractional velocity that was sustained for 360 minutes. The time course of the ability of hyperinsulinemia to increase HKII mRNA indicates that insulin is likely a physiological regulator of HKII expression in human skeletal muscle in vivo. FAU - Vogt, C AU - Vogt C AD - Department of Medicine, The University of Texas Health Science Center, San Antonio 78284-7886, USA. FAU - Ardehali, H AU - Ardehali H FAU - Iozzo, P AU - Iozzo P FAU - Yki-Jarvinen, H AU - Yki-Jarvinen H FAU - Koval, J AU - Koval J FAU - Maezono, K AU - Maezono K FAU - Pendergrass, M AU - Pendergrass M FAU - Printz, R AU - Printz R FAU - Granner, D AU - Granner D FAU - DeFronzo, R AU - DeFronzo R FAU - Mandarino, L AU - Mandarino L LA - eng GR - DK-24092/DK/NIDDK NIH HHS/United States GR - DK-46867/DK/NIDDK NIH HHS/United States GR - DK-47936/DK/NIDDK NIH HHS/United States GR - etc. PT - Clinical Trial PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Metabolism JT - Metabolism: clinical and experimental JID - 0375267 RN - 0 (Insulin) RN - 0 (Isoenzymes) RN - 0 (RNA, Messenger) RN - EC 2.4.1.11 (Glycogen Synthase) RN - EC 2.7.1.1 (Hexokinase) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Adult MH - Female MH - Gene Expression Regulation, Enzymologic/drug effects MH - Glucose/pharmacology MH - Glucose Clamp Technique MH - Glycogen Synthase/metabolism MH - Hexokinase/genetics/*metabolism MH - Humans MH - Hyperinsulinism/blood/metabolism MH - Insulin/blood/pharmacology MH - Isoenzymes/metabolism MH - Male MH - Muscle, Skeletal/drug effects/*enzymology MH - RNA, Messenger/metabolism MH - Time Factors EDAT- 2000/07/06 11:00 MHDA- 2000/07/25 11:00 CRDT- 2000/07/06 11:00 PHST- 2000/07/06 11:00 [pubmed] PHST- 2000/07/25 11:00 [medline] PHST- 2000/07/06 11:00 [entrez] AID - S0026-0495(00)80073-6 [pii] AID - 10.1053/meta.2000.6245 [doi] PST - ppublish SO - Metabolism. 2000 Jun;49(6):814-8. doi: 10.1053/meta.2000.6245.