Insulin enhances renal glucose excretion: relation to insulin sensitivity and sodium-glucose cotransport

Abstract

IntroductionInsulin regulates renal glucose production and utilization; both these fluxes are increased in type 2 diabetes (T2D). Whether insulin also controls urinary glucose excretion is not known.MethodsWe applied the pancreatic clamp technique in 12 healthy subjects and 13 T2D subjects. Each participant received a somatostatin infusion and a variable glucose infusion to achieve (within 1 hour) and maintain glycemia at 22 mmol/L for 3 hours; next, a constant insulin infusion (240 pmol/min/kg) was added for another 3 hours. Urine was collected separately in each period for glucose and creatinine determination.ResultsDuring saline, glucose excretion was lower in T2D than controls in absolute terms (0.49 (0.32) vs 0.69 (0.18) mmol/min, median (IQR), p=0.01) and as a fraction of filtered glucose (16.2 (6.4) vs 19.9 (7.5)%, p<0.001). With insulin, whole-body glucose disposal rose more in controls than T2D (183 (48) vs 101 (48) µmol/kgFFM/min, p<0.0003). Insulin stimulated absolute and fractional glucose excretion in controls (p<0.01) but not in T2D. Sodium excretion paralleled glucose excretion. In the pooled data, fractional glucose excretion was directly related to whole-body glucose disposal and to fractional sodium excretion (r=0.52 and 0.54, both p<0.01). In another group of healthy controls, empagliflozin was administered before starting the pancreatic clamp to block sodium-glucose cotransporter 2 (SGLT2). Under these conditions, insulin still enhanced both glucose and sodium excretion.ConclusionsAcute exogenous insulin infusion jointly stimulates renal glucose and sodium excretion, indicating that the effect may be mediated by SGLTs. This action is resistant in patients with diabetes, accounting for their increased retention of glucose and sodium, and is not abolished by partial SGLT2 inhibition by empagliflozin.

Impact of magnesium sulfate therapy in improvement of renal functions in high fat diet-induced diabetic rats and their offspring

“…In comparison to both NDC groups, insulin or MgSO 4 medication in both parents lowers GFR, which in turn lowers both parents' FE Na and FE G levels. The same pattern was observed in male children of diabetic parents and parents receiving MgSO 4 or insulin, Ferrannini et al showed that acute insulin infusion stimulates renal glucose and sodium excretion, and this effect may be mediated by sodium glucose transporter (SGLTs) 48 . FE Na can be useful to evaluate acute kidney failure.…”

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“…More recently, the combined use of noninvasive technology—PET scanning of [ 15 O]H 2 O and 14( R,S )-[ 18 F]fluoro-6-thia-heptadecanoate (an analog of short-chain FFA), computed tomography, and MRI—has made it possible to demonstrate higher FFA uptake in the cortical than in the medullary region and increased renal volume, blood flow, and FFA uptake in obese, insulin-resistant individuals ( 23 ). In insulin-resistant patients with type 2 diabetes, physiological hyperinsulinemia appears to reduce proximal tubular reabsorption of glucose and sodium ( 24 ).…”