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  • Song, X M (author)

5-Aminoimidazole-4-carboxamide ribonucleoside treatment improves glucose homeostasis in insulin-resistant diabetic (ob/ob) mice.

  • Article/chapterEnglish2002

Publisher, publication year, extent ...

  • 2002
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:gih-5020
  • https://urn.kb.se/resolve?urn=urn:nbn:se:gih:diva-5020URI
  • https://doi.org/10.1007/s001250200006DOI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • AIMS/HYPOTHESIS: The 5'AMP-activated protein kinase is an important mediator of muscle contraction-induced glucose transport and a target for pharmacological treatment of Type II (non-insulin-dependent) diabetes mellitus. The 5'AMP-activated protein kinase can be activated by 5-aminoimidazole-4-carboxamide ribonucleoside. We hypothesised that 5-aminoimidazole-4-carboxamide ribonucleoside treatment could restore glucose homeostasis in ob/ob mice.METHODS: Lean and ob/ob mice were given 5-aminoimidazole-4-carboxamide ribonucleoside (1 mg.g body wt(-1).day(-1) s.c) or 0.9 % NaCl (vehicle) for 1-7 days.RESULTS: Short-term 5-aminoimidazole-4-carboxamide ribonucleoside treatment normalised glucose concentrations in ob/ob mice within 1 h, with effects persisting over 4 h. After 1 week of daily injections, 5-aminoimidazole-4-carboxamide ribonucleoside treatment corrected hyperglycaemia, improved glucose tolerance, and increased GLUT4 and hexokinase II protein expression in skeletal muscle, but had deleterious effects on plasma non-esterified fatty acids and triglycerides. Treatment with 5-aminoimidazole-4-carboxamide ribonucleoside increased liver glycogen in fasted and fed ob/ob mice and muscle glycogen in fasted, but not fed ob/ob and lean mice. Defects in insulin-stimulated phosphatidylinositol 3-kinase and glucose transport in skeletal muscle from ob/ob mice were not corrected by 5-aminoimidazole-4-carboxamide ribonucleoside treatment. While ex vivo insulin-stimulated glucose transport was reduced in isolated muscle from ob/ob mice, the 5-aminoimidazole-4-carboxamide ribonucleoside stimulated response was normal.CONCLUSION/INTERPRETATION: The 5-aminoimidazole-4-carboxamide ribonucleoside mediated improvements in glucose homeostasis in ob/ob mice can be explained by effects in skeletal muscle and liver. Due to the apparently deleterious effects of 5-aminoimidazole-4-carboxamide ribonucleoside on the blood lipid profile, strategies to develop tissue-specific and pathway-specific activators of 5'AMP-activated protein kinase should be considered in order to improve glucose homeostasis.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Fiedler, M (author)
  • Galuska, D (author)
  • Ryder, J W (author)
  • Fernström, MariaKarolinska institutet(Swepub:gih)mariaf (author)
  • Chibalin, A V (author)
  • Wallberg-Henriksson, H (author)
  • Zierath, J R (author)
  • Karolinska institutet (creator_code:org_t)

Related titles

  • In:Diabetologia45:1, s. 56-650012-186X1432-0428

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