Highlights d CNS-Gipr KO mice are protected from diet-induced obesity and glucose intolerance d Acyl-GIP increases cFOS neuronal activity in key hypothalamic feeding centers d Acyl-GIP effects on body weight and food intake are absent/ blunted in CNS-mGipr KO mice d GLP-1/GIP dual-agonism loses superior potency over GLP-1 in CNS-mGipr KO mice.

Empagliflozin reduced blood glucose levels in a T1DM animal model. Empagliflozin combined with low-dose insulin showed comparable glucose-lowering efficacy to treatment with high-dose insulin. Our data suggest that empagliflozin is an efficacious adjunctive-to-insulin therapy with the clinical potential for the treatment of T1DM.

Renal nerves appear to be significantly involved in the mediation of glomerular hyperfiltration in experimental DM. If the kidney is prevented from sympathetic nerve stimulation, structural changes due to early diabetic nephropathy, i.e. glomerular enlargement, are abolished.

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The renal effects of the D3 receptor agonist R(+)-7-hydroxy-dipropyl-aminotetraline (7-OH-DPAT) were studied in anesthetized Sprague-Dawley rats using standard clearance experiments. 7-OH-DPAT infusion (0.01, 0.1, and 1.0 microg kg(-1) min(-1)) dose-dependently increased glomerular filtration rate (GFR) compared to baseline by a maximum of 20+/-2% while arterial blood pressure was not affected. Heart rate was not altered during the two lower doses of 7-OH-DPAT whereas a slight reduction occurred due to infusion of 1.0 microg kg(-1) min(-1). In contrast, higher doses of 7-OH-DPAT, starting from 3 microg kg(-1) min(-1), markedly influenced systemic hemodynamics. In addition to the hyperfiltration, 7-OH-DPAT (1.0 microg kg(-1) min(-1)) also induced a significant diuresis (27.7+/-4.3 microl min(-1) 100 g(-1) vs 16.2+/-5.4 microl min(-1) 100 g(-1)) and increased both absolute (3.30+/-0.58 micromol min(-1) 100 g(-1) vs 0.95+/-0.26 micromol min(-1) 100 g(-1)) and fractional sodium excretion (2.48+/-0.32% vs 0.79+/-0.19%). These changes in renal function were not modulated by pretreatment with the D2 receptor antagonist S(-)-sulpiride but abolished by the D3 antagonist 5,6-dimethoxy-2-(di-n-propylamino)indane (U-99194A). In coincidence with the action of 7-OH-DPAT on both glomerular and tubular function, reverse transcription-polymerase chain reaction (RT-PCR) revealed the expression of D3 receptors in both glomerular and tubular fractions of kidneys taken from Sprague-Dawley rats. These data indicate that D3 receptors in the kidney are involved in the regulation of renal hemodynamics and tubular function.