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

• 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.

Ämnesord

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)

Nyckelord

b2-adrenergic agonist

brown adipose tissue

skeletal muscle

type 2 diabetes mellitus

UCP1

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)