Prolonged b(2)-adrenergic agonist treatment improves glucose homeostasis in diet-induced obese UCP1(-/-) mice

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van Beek, Sten M. M. (author)

Prolonged b(2)-adrenergic agonist treatment improves glucose homeostasis in diet-induced obese UCP1(-/-) mice

Article/chapterEnglish2021

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American Physiological Society,2021
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LIBRIS-ID:oai:DiVA.org:su-194545
https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-194545URI
https://doi.org/10.1152/ajpendo.00324.2020DOI

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Language:English
Summary in:English

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Prolonged supplementation with the b2-agonist clenbuterol improves glucose homeostasis in diabetic rodents, likely via b2-adreno-ceptor (b2-AR)-mediated effects in the skeletal muscle and liver. However, since rodents have, in contrast to—especially diabetic—humans, substantial quantities of brown adipose tissue (BAT) and clenbuterol has affinity to b1- and b3-ARs, the contribution of BAT tothese improvements is unclear. Therefore, we investigated clenbuterol-mediated improvements in glucose homeostasis in uncouplingprotein 1-deficient (UCP1/) mice, lacking thermogenic BAT, versus wild-type (WT) mice. Anesthetized WT and UCP1/C57Bl/6 micewere injected with saline or clenbuterol and whole body oxygen consumption was measured. Furthermore, male WT and UCP1/C57Bl/6 mice were subjected to 17-wk of chow feeding, high-fat feeding, or high-fat feeding with clenbuterol treatment betweenweeks 13 and 17. Body composition was measured weekly with MRI. Oral glucose tolerance and insulin tolerance tests were per-formed in week 15 and 17, respectively. Clenbuterol increased oxygen consumption approximately twofold in WT mice. This increasewas blunted in UCP1/mice, indicating clenbuterol-mediated activation of BAT thermogenesis. High-fat feeding induced diabeto-genic phenotypes in both genotypes. However, low-dose clenbuterol treatment for 2 wk significantly reduced fasting blood glucoseby 12.9% in WT and 14.8% in UCP1/mice. Clenbuterol treatment improved glucose and insulin tolerance in both genotypes com-pared with HFD controls and normalized to chow-fed control mice independent of body mass and composition alterations.Clenbuterol improved whole body glucose homeostasis independent of UCP1. Given the low human abundancy of BAT, b2-AR ago-nist treatment provides a potential novel route for glucose disposal in diabetic humans.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Endokrinologi och diabetes hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Endocrinology and Diabetes hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Fysiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Physiology hsv//eng
b2-adrenergic agonist
brown adipose tissue
skeletal muscle
type 2 diabetes mellitus
UCP1

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Kalinovich, AnastasiaStockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut(Swepub:su)akali (author)
Schaart, Gert (author)
Bengtsson, ToreStockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut(Swepub:su)tbeng (author)
Hoeks, Joris (author)
Stockholms universitetInstitutionen för molekylär biovetenskap, Wenner-Grens institut (creator_code:org_t)

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In:American Journal of Physiology. Endocrinology and Metabolism: American Physiological Society320:3, s. E619-E6280193-18491522-1555

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