Cersosimo E, Molina P E, Abumrad N N
Department of Medicine, State University of New York at Stony Brook 11794-8154, USA.
Diabetes. 1997 Apr;46(4):643-6. doi: 10.2337/diab.46.4.643.
Recent in vivo studies have rekindled interest in the role of the kidney in glucose metabolism. We therefore undertook the present study to evaluate the contribution of the kidney to systemic glucose production and utilization rates during insulin-induced hypoglycemia using arteriovenous balance combined with a tracer technique. Ten days after the surgical placement of sampling catheters in the right and left renal veins and femoral artery and of an infusion catheter in the left renal artery of dogs, systemic and renal glucose kinetics were measured with the peripheral infusion of [6-3H]glucose. Renal blood flow was determined with a flowprobe. After baseline, six dogs received 2-h simultaneous infusions of peripheral insulin (4 mU x kg(-1) x min(-1)) and left intrarenal [6,6-2H]dextrose (14 micromol x kg(-1) x min(-1)) to achieve and maintain left renal normoglycemia during systemic hypoglycemia. Arterial glucose decreased from 5.3 +/- 0.1 to 2.2 +/- 0.1 mmol/l; insulin increased from 46 +/- 5 to 1,050 +/- 50 pmol/l; epinephrine increased from 130 +/- 8 to 1,825 +/- 50 pg/ml; norepinephrine increased from 129 +/- 6 to 387 +/- 15 pg/ml; and glucagon increased from 52 +/- 2 to 156 +/- 12 pg/ml (all P < 0.01). Systemic glucose appearance increased from 16.6 +/- 0.4 micromol x kg(-1) x min(-1) in the baseline to 24.2 +/- 0.6 micromol x kg(-1) x min(-1) during hypoglycemia when endogenous glucose production was 10.2 +/- 1.0 micromol x kg(-1) x min(-10 (P < 0.01). In the baseline, the liver accounted for 80% (13.3 +/- 0.8 micromol x kg(-1) x min(-1)) and each kidney contributed 10% (1.6 +/- 0.2 micromol x kg(-1) x min(-1)) to endogenous glucose production. During hypoglycemia, however, hepatic glucose production decreased to 4.0 +/- 0.4 micromol x kg(-1) x min(-1), whereas right renal glucose production doubled to 3.2 +/- 0.2 micromol x kg(-1) x min(-1) (P < 0.01). Left renal glucose production was 17 +/- 2 micromol x kg(-1) x min(-1), 14 of which were derived from the exogenous infusion. These results indicate that glucose production by the kidney is stimulated by counterregulatory hormones and represents an important component of the body's defense against insulin-induced hypoglycemia.
近期的体内研究重新引发了人们对肾脏在葡萄糖代谢中作用的兴趣。因此，我们开展了本研究，采用动静脉平衡结合示踪技术，评估胰岛素诱导低血糖期间肾脏对全身葡萄糖生成和利用率的贡献。在给犬的右、左肾静脉和股动脉置入采样导管以及在左肾动脉置入输注导管10天后，通过外周输注[6-³H]葡萄糖来测量全身和肾脏的葡萄糖动力学。用血流探头测定肾血流量。在基线期后，6只犬同时接受2小时外周胰岛素（4 mU·kg⁻¹·min⁻¹）和左肾内[6,6-²H]葡萄糖（14 μmol·kg⁻¹·min⁻¹）输注，以在全身低血糖期间实现并维持左肾正常血糖水平。动脉葡萄糖从5.3±0.1 mmol/L降至2.2±0.1 mmol/L；胰岛素从46±5 pmol/L升至1050±50 pmol/L；肾上腺素从130±8 pg/ml升至1825±50 pg/ml；去甲肾上腺素从129±6 pg/ml升至387±15 pg/ml；胰高血糖素从52±2 pg/ml升至156±12 pg/ml（均P<0.01）。全身葡萄糖出现率从基线期的16.6±0.4 μmol·kg⁻¹·min⁻¹增加至低血糖期间的24.2±0.6 μmol·kg⁻¹·min⁻¹，此时内源性葡萄糖生成量为10.2±1.0 μmol·kg⁻¹·min⁻¹（P<0.01）。在基线期，肝脏对内源性葡萄糖生成的贡献率为80%（13.3±0.8 μmol·kg⁻¹·min⁻¹），每个肾脏的贡献率为10%（1.6±0.2 μmol·kg⁻¹·min⁻¹）。然而，在低血糖期间，肝脏葡萄糖生成量降至4.0±0.4 μmol·kg⁻¹·min⁻¹，而右肾葡萄糖生成量增加一倍，至3.2±0.2 μmol·kg⁻¹·min⁻¹（P<0.01）。左肾葡萄糖生成量为17±2 μmol·kg⁻¹·min⁻¹，其中14 μmol来自外源性输注。这些结果表明，肾脏的葡萄糖生成受到反调节激素的刺激，是机体抵御胰岛素诱导低血糖的重要组成部分。
