Induction of insulin resistance in normal adipose tissue by uremic human serum

McCaleb, Michael L.; Mevorach, Robert A.; Freeman, Richard B.; Izzo, Margaret S.; Lockwood, Dean H.

doi:10.1038/ki.1984.33

Cited by 38 publications

(11 citation statements)

References 24 publications

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“…Amongst these is insulin resistance [6], which has been characterized at the postreceptor level, and also reduced activities of lipoprotein lipase [7] and hepatic triglyceride lipase. A reduction in the ability of insulin to stimulate hexose uptake by uraemic rat adipo cytes has been found [8], and also uraemic human serum can induce an insulin-resistant state in normal rat adipo cytes [9]. These findings, together with the observatioi that glucose utilization in uraemic man is improved by dialysis therapy [10], suggest that uraemia per se is an important factor in the genesis of the reduction in body fat found in the subtotally nephrectomized animals.…”

Section: Discussionsupporting

confidence: 52%

Body Composition Changes in the Subtotally Nephrectomized Rat Fed Differing Dietary Proteins

Williams

Walls

1989

Nephron

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Changes in body composition are found in chronic uraemia, but it is unclear if this results from poor nutrient intake or is a consequence of impaired renal function. To investigate this question, 31 female Wistar rats were allocated to undergo subtotal nephrectomy or sham operation and were fed diets of either 24% casein or 24% soya protein. Three months later measurements of inulin clearance were undertaken in the conscious animal and the carcass subsequently analyzed for body water and body fat. Subtotally nephrectomized animals had a significantly greater proportion of body water (p < 0.001) and a lesser proportion of body fat (p < 0.001) than control animals, and a significant correlation was found between glomerular filtration rate and body fat content (24% casein diet: r = 0.96; 24% soya diet: r = 0.71). The dietary protein source appeared not to influence the body composition. These results support the concept that altered body composition in uraemia is due to renal dysfunction rather than altered nutrient intake.

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Section: Discussionsupporting

confidence: 52%

Body Composition Changes in the Subtotally Nephrectomized Rat Fed Differing Dietary Proteins

Williams

Walls

1989

Nephron

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“…It has been suggested that the mechanism may be related to the presence of an antiinsulin peptide in uremic serum that is dialyzable (22,23). Because, as pointed out previously, chiro-inositol increased in the urine of patients with renal disease who are not diabetic (1), a renal defect alone is unlikely to explain either the widespread deficiency of chiro-inositol mediator in the tissues examined or the differences in pH 2.0 mediator bioactivity seen in the dialysates.…”

Section: Methodsmentioning

confidence: 91%

chiro-inositol deficiency and insulin resistance: a comparison of the chiro-inositol- and the myo-inositol-containing insulin mediators isolated from urine, hemodialysate, and muscle of control and type II diabetic subjects.

Asplin

Galasko

Larner

1993

Proc. Natl. Acad. Sci. U.S.A.

162

145

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chiro-and myo-Inositols are major components of the two inositol phosphoglycan mediators of insulin action. Previous work in this laboratory has shown hypo-chiroinositoluria in type H diabetic subjects and decreased chiroinositol in mediator prepared from skeletal-muscle biopsies of Pima Indian diabetic subjects together with increased myoinositol concentrations. Because mediator bioactivity was not previously examined, we decided to isolate the two types of insulin mediator from hemodialysate, urine, and autopsy muscle to investigate their bioactivity in control and type H diabetic subjects. Human mediator fractions were isolated at pH 2.0 and pH 1.3 from hemodialysate, urine, and autopsy muscle of type II diabetic subjects and nondiabetic control subjects. Mediators were assayed for bioactivity, and the relative chiroinositol/myo-inositol concentration ratio was determined for the mediator pH 2.0 samples by using HPLC or GC/MS. Regardless of source, the chiro-inositol-containing mediator pH 2.0 fractions from type H diabetic subjects were markedly less active than those from controls (50% or less) (P < 0.05).In addition, the chiro-inositol/myo-inositol ratio in samples from type H subjects was signficantly reduced (1/3-1/9) compared with controls (P < 0.05 for hemodialysate and P < 0.01 for muscle samples). In contrast, no difference in bioactivity was seen in myo-inositol-containing mediator pH 1.3 samples isolated from the same type II diabetic and control subjects. In type H diabetes there is a generalized deficiency of chiro-inositol mediator in the body in terms of both decreased chiro-inositol mediator (pH 2.0) bioactivity and chiro-inositol content.

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“…In fact, it has been reported that epididymal fat pads from uremic rats can recover from an insu lin-resistant state when cultured for 20 h in a normal medium [42]. In addition, incubation of uremic serum with normal rat adipose tissue induces insulin resistance [43] and sera from uremic patients inhibit basal utiliza tion of glucose by muscle and erythrocytes [44][45][46].…”

Section: Discussionmentioning

confidence: 99%

Insulin Binding and Glycolytic Activity in Erythrocytes from Dialyzed and Nondialyzed Uremic Patients

Weisinger¹,

Contreras²,

Cajias³

et al. 1988

Nephron

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Insulin resistance in uremia has been attributed to impaired hormone-receptor binding or to postbinding defects. Oral glucose tolerance tests, insulin binding, and in vitro glycolytic activity were studied in purified red blood cells from normal control subjects (C) and from uremic patients belonging to three groups: nondialyzed (U), on chronic hemodialysis (HD), and on continuous ambulatory peritoneal dialysis (CAPD). Glucose intolerance and hyperinsulinemia were demonstrated in all groups of patients. Maximal specific binding of ¹²⁵I-insulin to erythrocytes, kinetically derived receptor numbers per cell, and affinity constants for insulin binding did not differ between control and patient groups. No correlation was found between the degree of glucose intolerance and insulin binding parameters. Basal lactate production by erythrocytes incubated invitro was significantly higher in U and HD patients than in Cwhereas CAPD patients did not differ from C in this respect. Addition of 1 mI dibutiryl-cAMP and 0.5 mM isobutyl-methyl-xanthine during incubation of erythrocytes caused an increase in the rate of lactate production that was similar in magnitude in the U, HD and C groups, whereas cells from CAPD subjects showed a significantly larger absolute response to these compounds after 1 h of incubation. There was no evidence of impairment of glycolytic capacity in red blood cells from uremic patients. In addition, no correlation was found between the degree of glucose intolerance and basal or stimulated lactate production by erythrocytes. Our results obtained in human erythrocytes suggest that the insulin resistance observed in uremia does not involve a defect in hormone binding or in the intracellular capacity to utilize glucose through glycolysis.

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Induction of insulin resistance in normal adipose tissue by uremic human serum

Cited by 38 publications

References 24 publications

Body Composition Changes in the Subtotally Nephrectomized Rat Fed Differing Dietary Proteins

Body Composition Changes in the Subtotally Nephrectomized Rat Fed Differing Dietary Proteins

chiro-inositol deficiency and insulin resistance: a comparison of the chiro-inositol- and the myo-inositol-containing insulin mediators isolated from urine, hemodialysate, and muscle of control and type II diabetic subjects.

Insulin Binding and Glycolytic Activity in Erythrocytes from Dialyzed and Nondialyzed Uremic Patients

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