Glyburide Regulates UCP1 Expression in Adipocytes Independent of KATP Channel Blockade

State-dependent inhibition of the mitochondrial KATP channel by glyburide and 5-hydroxydecanoate.

The mitochondrial KATP channel (mitoKATP) is hypothesized to be the receptor for the cardioprotective effects of K+ channel openers (KCO) and for the blocking of cardioprotection by glyburide and 5-hydroxydecanoate (5-HD). Studies on glyburide have indicated that this drug is inactive in isolated mitochondria. No studies of the effects of 5-HD on isolated mitochondria have been reported. This p...

Activation of the KATP Channel-Independent Signaling Pathway

The T3 receptor beta1 isoform regulates UCP1 and D2 deiodinase in rat brown adipocytes.

Brown adipose tissue (BAT) thermogenesis increases when uncoupling protein-1 (UCP1) is activated adrenergically and requires T3. In humans, UCP1 activation in BAT seems involved in body weight maintenance. BAT type 2 deiodinase (D2) increases in response to adrenergic agents, producing the T3 required for UCP1 expression. T3 actions are mediated by thyroid hormone nuclear T3 receptors (TR), TRα...

Independent trafficking of KATP channel subunits to the plasma membrane.

KATP channels are unique in requiring two distinct subunits (Kir6.2, a potassium channel subunit) and SUR1 (an ABC protein) for generation of functional channels. To examine the cellular trafficking of KATP channel subunits, green fluorescent protein (GFP) was tagged to the cytoplasmic N or C terminus of SUR1 and Kir6. 2 subunits and to the C terminus of a dimeric fusion between SUR1 and Kir6.2...

FGF21 mimetic antibody stimulates UCP1-independent brown fat thermogenesis via FGFR1/βKlotho complex in non-adipocytes

OBJECTIVE Fibroblast Growth Factor 21 (FGF21) is a potent stimulator of brown fat thermogenesis that improves insulin sensitivity, ameliorates hepatosteatosis, and induces weight loss by engaging the receptor complex comprised of Fibroblast Growth Factor Receptor 1 (FGFR1) and the requisite coreceptor βKlotho. Previously, recombinant antibody proteins that activate the FGFR1/βKlotho complex wer...