Insulin regulation of renal glucose metabolism in conscious dogs.

Cersósimo, Eugênio; Judd, Robert L.; Miles, John M.

doi:10.1172/jci117270

Cited by 123 publications

(97 citation statements)

References 43 publications

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“…In addition, experiments in laboratory animals and human subjects have indicated that the kidney plays an important role in glucose metabolism (25,26). Animal and human studies indicate that acute renal failure results in a reduction in the systemic removal of insulin (27).…”

Section: Discussionmentioning

confidence: 99%

Insulin Resistance and Risk of Chronic Kidney Disease in Nondiabetic US Adults

Chen¹,

Muntner²,

Hamm³

et al. 2003

Journal of the American Society of Nephrology

344

238

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Abstract. This study examined the relationship of fasting serum glucose, insulin, C-peptide, glycosylated hemoglobin A (HbA1c), and Homeostasis Model Assessment (HOMA)-insulin resistance to risk of chronic kidney disease (CKD) among 6453 persons without diabetes (fasting glucose Ͻ126 mg/dl and not taking diabetes medication) who participated in the Third National Health and Nutrition Examination Survey and were aged 20 yr or older. CKD was defined as an estimated GFR Ͻ60 ml/min per 1.73 m 2 . The prevalence of CKD was significantly and progressively higher with increasing levels of serum insulin, C-peptide, HbA1c, and HOMA-insulin resistance. After adjustment for potential confounding variables, the odds ratio of CKD for the highest compared with the lowest quartile was 4.03 (95% confidence interval [CI], 1.81 to 8.95; P ϭ 0.001), 11.4 (95% CI, 4.07 to 32.1; P Ͻ 0.001), 2.67 (95% CI, 1.31 to 5.46; P ϭ 0.002), and 2.65 (95% CI, 1.25 to 5.62; P ϭ 0.008) for serum insulin, C-peptide, HbA1c levels, and HOMA-insulin resistance, respectively. For a one SD higher level of serum insulin (7.14 U/ml), C-peptide (0.45 ⌬mol/ ml), HbA1c (0.52%), and HOMA-insulin resistance (1.93), the odds ratio (95% CI) of CKD was 1.35 (1.16 to 1.57), 2.78 (2.25 to 3.42), 1.69 (1.28 to 2.23), and 1.30 (1.13 to 1.50), respectively. These findings combined with knowledge from previous studies suggest that the insulin resistance and concomitant hyperinsulinemia are presented in CKD patients without clinical diabetes. Further studies into the causality between insulin resistance and CKD are warranted.Diabetic nephropathy remains the leading cause of end-stage renal disease (ESRD) in western populations (1) and accounts for over 40% of new cases of ESRD each year in the United States (2-4). The prevalence of diabetes has been increasing progressively in the US and other countries, and the number of adults with diabetes in the world is projected to increase to approximately 300 million in the year 2025 (5). As a consequence, diabetic ESRD is expected to become increasingly prevalent in the future (6). Patients with ESRD suffer from poor quality of life and shorter life expectancy compared with individuals of the same age in the general population (3,4). Those with diabetic ESRD have a much less favorable outcome than their counterparts with nondiabetic ESRD (4,7). Prevention of diabetes-related kidney disease is a key to decreasing the societal and personal burden of illness due to ESRD.Insulin resistance and compensatory hyperinsulinemia have been associated with hypertension, hyperuricemia, increased levels of serum triglyceride, smaller denser LDL particles, circulating plasminogen activator inhibitor, and decreased levels of HDL (8,9). Furthermore, insulin resistance has been an underlying cause of type 2 diabetes and arteriosclerotic vascular disease (10 -12). Several small clinical studies have noted insulin resistance in nondiabetic patients with mild renal dysfunction (13-15). However, there are sparse data on the relationship among insul...

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Section: Discussionmentioning

confidence: 99%

Insulin Resistance and Risk of Chronic Kidney Disease in Nondiabetic US Adults

Chen¹,

Muntner²,

Hamm³

et al. 2003

Journal of the American Society of Nephrology

344

238

View full text Add to dashboard Cite

show abstract

“…The renal contribution to endogenous glucose production has been a matter of much controversy [4][5][6][7][8][9][10][11][12]28]. Much of the confusion in all likelihood has arisen from the fact that measurements across the renal bed, because of the high renal blood flow of around 1 l/min, are highly susceptible to methodological imprecision as regards analysis of differences in arteriovenous glucose concentrations and dilution of tracers.…”

Section: Discussionmentioning

confidence: 99%

“…Several reports have suggested that in addition the kidney may be an important component in the regulation of intermediary metabolism, in particular glucose metabolism [4]. This renewed interest in the metabolic role of the kidney was fuelled by a study by Cersosimo et al [5] who used arteriovenous balance and isotopic dilution techniques to report that in postabsorptive dogs renal glucose utilisation and production each accounted for close to 30% of total glucose turnover in the presence of net balances close to zero. More recent studies in humans have reported that the renal contribution to postabsorptive whole-body glucose production may amount to between 15 and 30%, that glutamine appears to be an important precursor for renal gluconeogenesis and that renal glucose production increases in response to epinephrine and hypoglycaemia and decreases during insulin exposure [6][7][8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Renal amino acid, fat and glucose metabolism in type 1 diabetic and non-diabetic humans: effects of acute insulin withdrawal

et al. 2006

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Aims/hypothesis: The aim of this study was to test the hypothesis that type 1 diabetes alters renal amino acid, glucose and fatty acid metabolism. Materials and methods: We studied five C-peptide-negative, type 1 diabetic subjects during insulin replacement (glucose 5.6 mmol/l) and insulin deprivation (glucose 15.5 mmol/l) and compared them with six non-diabetic subjects. Leucine, phenylalanine, tyrosine, glucose and palmitate tracers were infused after an overnight fast and samples were obtained from the renal vein, femoral vein and femoral artery. Results: Insulin deprivation significantly increased wholebody fluxes (20-25%) of phenylalanine, tyrosine and leucine, and leucine oxidation (50%). Kidney contributed 5-10% to the whole-body leucine and phenylalanine flux. A net uptake of phenylalanine, conversion of phenylalanine to tyrosine (5 μmol/min) and net release of tyrosine (∼5 μmol/min) occurred across the kidney. Whole-body (three-fold) and leg (two-fold) leucine transamination increased but amino acid metabolism in the kidney did not alter with diabetes or insulin deprivation. Insulin deprivation doubled endogenous glucose production, renal glucose production was unaltered by insulin deprivation and diabetes (ranging between 100 and 140 μmol/min).Renal palmitate exchange was unaltered by insulin deprivation. Conclusions/interpretation: In conclusion, kidney postabsorptively accounts for 5-10% of whole-body protein turnover, 15-20% of leucine transamination and 10-15% of endogenous glucose production, and actively converts phenylalanine to tyrosine. During insulin deprivation, leg becomes a major site for leucine transamination but insulin deprivation does not affect renal phenylalanine, leucine, palmitate or glucose metabolism. Despite its key metabolic role, insulin deprivation in type 1 diabetic patients does not alter many of these metabolic functions.

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“…At ϳ8:00 AM, an infusion of p-aminohippuric acid (12 mg/min) was started for determination of renal blood flow (RBF). In addition, five subjects also received an infusion of [9, H]palmitate; their baseline data have been previously reported (41). Between 8:00 and 9:00 AM, a renal vein was catheterized under fluoroscopy and the position of the catheter tip ascertained by injecting a small amount of iodinated contrast material.…”

Section: Subjectsmentioning

confidence: 99%

“…However, it should be pointed out that bias in the handling of data in some of these studies (39-42, 45, 49, 50, 52) may have led to an overestimation of renal glucose release (28). Recent studies also indicate that renal release of glucose, like that of the liver, is regulated by insulin (9,40) and counterregulatory hormones (10,39,49). These findings suggest that the kidney may also be involved in postprandial glucose homeostasis.…”

mentioning

confidence: 99%

Role of human liver, kidney, and skeletal muscle in postprandial glucose homeostasis

Meyer¹,

Dostou²,

Welle

et al. 2002

American Journal of Physiology-Endocrinology and Metabolism

235

163

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. Role of human liver, kidney, and skeletal muscle in postprandial glucose homeostasis. Am J Physiol Endocrinol Metab 282: E419-E427, 2002; 10.1152/ ajpendo.00032.2001.-Recent studies indicate a role for the kidney in postabsorptive glucose homeostasis. The present studies were undertaken to evaluate the role of the kidney in postprandial glucose homeostasis and to compare its contribution to that of liver and skeletal muscle. Accordingly, we used the double isotope technique along with forearm and renal balance measurements to assess systemic, renal, and hepatic glucose release as well as glucose uptake by kidney, skeletal muscle, and splanchnic tissues in 10 normal volunteers after ingestion of 75 g of glucose. We found that, during the 4.5-h postprandial period, 22 Ϯ 2 g (30 Ϯ 3% of the ingested glucose) were initially extracted by splanchnic tissues. Of the remaining 53 Ϯ 2 g that entered the systemic circulation, 19 Ϯ 3 g were calculated to have been taken up by skeletal muscle and 7.5 Ϯ 1.7 g by the kidney (26 Ϯ 3 and 10 Ϯ 2%, respectively, of the ingested glucose). Endogenous glucose release during the postprandial period (16 Ϯ 2 g), calculated as the difference between overall systemic glucose appearance and the appearance of ingested glucose in the systemic circulation, was suppressed 61 Ϯ 3%. Surprisingly, renal glucose release increased twofold (10.6 Ϯ 2.5 g) and accounted for ϳ60% of postprandial endogenous glucose release. Hepatic glucose release (6.7 Ϯ 2.2 g), the difference between endogenous and renal glucose release, was suppressed 82 Ϯ 6%. These results demonstrate a hitherto unappreciated contribution of the kidney to postprandial glucose homeostasis and indicate that postprandial suppression of hepatic glucose release is nearly twofold greater than had been calculated in previous studies (42 Ϯ 4%), which had assumed that there was no renal glucose release. We postulate that increases in postprandial renal glucose release may play a role in facilitating efficient liver glycogen repletion by permitting substantial suppression of hepatic glucose release.gluconeogenesis; glycogenolysis; glucose disposal CONSIDERABLE INFORMATION has recently accumulated regarding postprandial glucose homeostasis. It appears that about one-third of ingested carbohydrate is immediately taken up by splanchnic tissues (5, 22, 33-35, 37, 38, 44, 60). Of the remaining two-thirds of the ingested carbohydrate that enters the systemic circulation, some is extracted by the liver (23), but most is taken up by peripheral tissues. Limb balance measurements indicate that skeletal muscle is the predominant site for this peripheral glucose disposal, being responsible for about one-fourth of the ingested carbohydrate (5, 26, 33-35, 37, 38, 44). The fate of the remaining 40% of the ingested carbohydrate is less clear.In addition to tissue uptake of ingested carbohydrate, another important factor for postprandial glucose homeostasis is suppression of the release of glucose endogenously produced by gluconeogenesis and breakdown of ...

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Insulin regulation of renal glucose metabolism in conscious dogs.

Cited by 123 publications

References 43 publications

Insulin Resistance and Risk of Chronic Kidney Disease in Nondiabetic US Adults

Insulin Resistance and Risk of Chronic Kidney Disease in Nondiabetic US Adults

Renal amino acid, fat and glucose metabolism in type 1 diabetic and non-diabetic humans: effects of acute insulin withdrawal

Role of human liver, kidney, and skeletal muscle in postprandial glucose homeostasis

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