Sustained improvement in glucose homeostasis in lean and obese mice following chronic administration of the β₃ agonist SR 58611A

Abstract

1 Acute SR 58611A (0.25 mg kg 71 ), was eective in reducing the blood glucose response to a glucose tolerance test (GTT) in normal lean (control) and spontaneously obese/diabetic CBA/Ca mice and to be equipotent to 1.25 mg kg 71 glibenclamide in lean mice. 2 Neither brown (BAT) nor white (WAT) adipose tissue lipogenesis was altered by acute SR 58611A (2 ± 8 mg kg 71 ) in lean mice, but both increased signi®cantly at the higher doses in the obese mice. 3 Acute SR 58611A produced a hypoglycaemia 40 min after dosing in lean and obese animals, the duration and potency of which was less than that of glibenclamide. Plasma insulin levels increased 20 min after acute SR 58611A and glibenclamide in lean and obese mice. 4 Chronic treatment (0.25 mg kg 71 , 15 days) with SR 58611A increased its eectiveness in improving glucose tolerance, but did not aect the body weight (BW) or food intake of either lean or obese mice. 5 Acute and chronic SR 58611A prolonged the hypoglycaemic eect of exogenous insulin in lean but not obese mice. 6 In fed and fasted lean mice and in fasted obese mice chronic SR 58611A produced an acute hypoglycaemia 30 min post administration which was greater than after a single dose. 7 SR 58611A maintained its eectiveness in improving glucose tolerance in lean and obese mice over a dosing period of 15 days. The improvement in glucose tolerance was achieved at a dose less than that required to stimulate adipose tissue lipogenesis and which did not aect food intake or body weight.

Cytochrome P450 epoxygenase-derived epoxyeicosatrienoic acids contribute to insulin sensitivity in mice and in humans

“…; 0.083 mg/ml in sterile saline [154 mmol/l NaCl] + 0.2% wt./vol. DMSO; Merck Millipore, Darmstadt, Germany) was administered and saphenous vein blood was collected before and at 15 min for insulin assay [21, 22]. …”

G Protein–Coupled Receptors Targeting Insulin Resistance, Obesity, and Type 2 Diabetes Mellitus

“…mRNA encoding b 3 -adrenoceptors is found in the bladder, heart, gastrointestinal tract, and adipose tissue, with particularly high concentrations in rodent brown fat (Evans et al, 1996(Evans et al, , 1999Emilsson et al, 1998). Although several studies have examined effects of b 3 -adrenoceptor agonists on lipolysis and heat production in brown fat, it was apparent even in early studies that b 3 -adrenoceptor (or atypical b-adrenoceptor) agonists improve glucose tolerance and insulin sensitivity (Cawthorne et al, 1984;Sennitt et al, 1985;Williams et al, 1999). Recent studies suggest that the improvement in insulin sensitivity is related to downregulation of TNF-a expression (Ghorbani et al, 2012).…”

Improving glycogenesis in Streptozocin (STZ) diabetic mice after administration of green algae Chlorella

“…Mice were lightly anesthetized with diethyl ether prior to drug administration by oral gavage. The test dose for glibenclamide (as positive control) was 2.5 mg/kg according to previous work (Williams et al, 1999a;Cherng and Shih, 2005b) and insulin was 2.5 IU/kg (Williams et al, 1999b;Cherng and Shih, 2005b).…”