Project: Research project

Project Details


This project will exmine the role of the kidney in glucose metabolism in
nondiabetic and diabetic dogs. It will establish the contribution of
renal glucose production (RGP) and renal glucose utilization (RGU) to
systemic glucose kinetics under physiologic conditions and in diabetes,
and to investigate the hormonal and substrate regulation of renal glucose
turnover in vivo. Our preliminary data indicate that RGP equals RGU and
accounts for about 30% of endogenous glucose appearance in the
postabsorptive dog. We hypothesize that glucose handling by the kidney
is critical to fuel homeostasis and that the renal response to insulin
deficiency plays an important role in the hyperglycemia of diabetes.
First, we plan to test whether autoregulation by glucose is operative in
the kidney as it is in the liver, and whether hyperglycemia which
saturates tubular reabsorption of glucose coincides both with maximal
stimulation of RGU and suppression of RGP, rendering the effect of
hyperinsulinemia on these processes redundant. Since gluconeogenesis is
increased in diabetes, we will determine whether increased free fatty
acid and amino acid availability, typically seen with insulin deficiency,
stimulate RGP and gluconeogenesis, and whether these are suppressed by
hyperinsulinemia. Hypoglycemia occurs frequently in patients with
chronic renal failure, particularly in diabetes. We will test the
hypotheses that RGP increases and RGU decreases in the recovery from
hypoglycemia induced by insulin. Finally, we will study the effects of
short-term insulin deficiency on renal glucose metabolism and its
response to peripheral and intraportal insulin replacement. All studies
will be performed in conscious dogs; 10-14 days prior to the experiment,
catheters will be implanted in the left renal vein, left renal artery and
the femoral artery under general anesthesia; doppler flow probes will be
placed around the left and right renal arteries for subsequent continuous
measurement of renal blood flow. Selected dogs will undergo total
pancreatectomy and catheters will be placed in the portal vein. Primed
constant peripheral infusions of [3-3H]glucose, [2-14C]glycerol and
insulin, together with intrarenal infusion will be utilized. This research will provide considerable additional information regarding
the contribution of RGP and RGU to systemic glucose metabolism in the
postabsorptive state and in uncontrolled diabetes mellitus. In addition,
the proposed studies will characterize in detail the regulation of RGP
and RGU by free fatty acids, amino acids, insulin and glucose itself.
We anticipate that these studies will lead to analogous studies in
nondiabetic and diabetic humans.
Effective start/end date9/30/948/31/00


  • National Institutes of Health: $118,045.00
  • National Institutes of Health: $94,476.00


  • Medicine(all)


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