Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetes mellitus is associated with enhanced passive intestinal uptake of cholesterol and fatty acids. In order to determine the basis for these changes in intestinal permeability, the jejunal morphology and the lipid content of purified brush border membranes (BBM) were measured in fasted and fed control (C) and streptozotocin diabetic (DM) rats. There was no difference between C and DM in BBM sucrase or alkaline phosphatase; fasting had no effect on BBM enzymes in C, but in DM fasting was associated with increased sucrase activity per length of jejunum. In C fasting was associated with higher levels of BBM total phospholipid, lecithin, choline and amine phospholipids, whereas fasting in DM was associated with higher BBM cholesterol and lower free fatty acids. In the fasting DM, there was a greater villus and mucosal surface area than in the fasting C. A previous study demonstrated that with fasting in DM versus C, cholesterol uptake was unchanged, but when animals were fed, cholesterol and fatty acid uptake were greater into the jejunum of fed DM as compared with fed C. In the BBM of fed DM as compared with C, there was a significant increase in total phospholipid, lecithin, phosphatidyl ethanolamine, choline and amine phospholipids, and phospholipid/cholesterol ratio. Thus, (1) fasting is associated with changes in intestinal morphology, BBM lipids; (2) the effect of fasting is different in DM and C; (3) the enhanced uptake of lipids into the jejunum of fed diabetic rats is not due to changes in villus morphology, but may be due to alterations in the BBM phospholipids.
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PMID:Intestinal brush border membrane marker enzymes, lipid composition and villus morphology: effect of fasting and diabetes mellitus in rats. 286 16

To examine the pattern and mechanisms of enhanced intestinal nutrient absorption in diabetes, we measured intestinal transport of 3-O-methylglucose (3OMG), l-alanine (ALA), and SO4 in male Lewis rats made diabetic with streptozocin. Diabetes enhanced 3OMG absorption fivefold in ileum and threefold in jejunum; ALA absorption increased twofold in ileum but not at all in jejunum; ileal SO4 transport was unaffected. Increases in 3OMG and ALA transport were due solely to increases in maximum velocity. The enhancement of ileal glucose absorption was half-maximal in 40-45 d, could be reversed by 10 d of treatment with insulin and did not result from adrenergic denervation. The density of glucose carriers per milligram brush border protein (measured as [3H]phlorizin binding sites) was not altered but there was a sixfold increase in the number of glucose-inhibitable [3H]phlorizin-binding sites in the intact epithelium. Generalized mucosal hypertrophy accounted for less than 30% of this increase. We conclude that the intestine adapts to streptozocin-induced diabetes through recruitment of additional brush border carriers for sugar, probably in the midvillus-to-crypt region.
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PMID:Intestinal adaptation to diabetes. Altered Na-dependent nutrient absorption in streptozocin-treated chronically diabetic rats. 295 60

(Na+ + K+)-activated adenosine triphosphatase activity in the mucosal homogenate of rat small intestine estimated under conditions of experimental diabetes, application of corticosteroids, adrenalectomy or inhibition of adrenocortical function suggests a general parallelism between the capacity for monosaccharide absorption and enzyme activity. Studying the kinetic parameters it has been found that the maximal velocities of monosaccharide uptake as well as of (Na+ + K+)-activated adenosine triphosphatase reaction are significantly different, whereas sugar concentrations for halfmaximal transport velocities and enzyme-substrate affinity constants remain unaltered. From studies with purified brush borders and basolateral plasma membranes it has been shown that the activity changes were caused exclusively by that part of (Na+ + K+)-activated adenosine triphosphatase which is localized in the basolateral plasma membranes. The enzyme activity in the brush border region remains unchanged. These findings support a concept of intestinal transport mechanism which suggests that the basolateral part of (Na+ + K+)-activated adenosine triphosphatase is responsible for metabolic energy supply.
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PMID:Effect of diabetes and adrenocortical state on intestinal transport capacity and (Na+ + K+)-activated adenosine triphosphatase activity. 302 48

Little is known about hormonal regulation of substrate transport and metabolism in the mucosal lining of the small intestine. Because insulin regulates these functions in other tissues by binding to its receptor, we have investigated the presence of insulin receptors in canine small intestinal mucosa with basolateral membranes (BLM) and brush border membranes (BBM) prepared by sorbitol density centrifugation. A14-[125I]iodoinsulin was used to study binding and structural characteristics of specific insulin receptors in BLM. Analysis of receptors in BLM identified binding sites with high affinity (Kd 88 pM) and low capacity (0.4 pmol/mg protein) as well as with low affinity (Kd 36 nM) and high capacity (4.7 pmol/mg protein). Binding was time, temperature, and pH dependent, and 125I-labeled insulin dissociation was enhanced in the presence of unlabeled insulin. Cross-reactivity of these receptors to proinsulin, IGF-II, and IGF-I was 4, 1.8, and less than 1%, respectively. Covalent cross-linking of labeled insulin to BLM insulin receptors with disuccinimidyl suberate revealed a single 135,000-Mr band that was completely inhibited by unlabeled insulin. There was a 16-fold greater specific binding of insulin to BLM (39.0 +/- 2.4%) than to BBM (2.5 +/- 0.6%). These results demonstrate the presence of a highly specific receptor for insulin on the vascular, but not the luminal, surface of the small intestinal mucosa in dogs, and suggest that insulin may play an important role in the regulation of gastrointestinal physiology.
Diabetes 1987 Oct
PMID:Identification and characterization of insulin receptors in basolateral membranes of dog intestinal mucosa. 330 83

Immune complex-mediated injury has been postulated to contribute to diabetic microangiopathy. To test this hypothesis, immune complex disease was induced in both insulin-deficient (I-) and insulin-treated (I+) rats with streptozocin-induced diabetes mellitus (DM), and the rats were compared with their respective controls. Heymann nephritis (HN), an animal model of membranous nephropathy, was induced in rats by immunization with proximal renal tubular brush border antigen. In addition to the homogeneous mesangial deposits of IgG that developed in diabetic rats, diabetic rats with immune injury also developed immune deposits of IgG and tubular antigen. Diabetic animals with Heymann nephritis developed more intense granular mesangial and capillary wall immune deposits, detected by immunofluorescence (ranked-sums test, P = .002) and electron microscopy. Mesangial immune deposits were associated with mesangial hypercellularity, determined by counting nuclei per glomerular cross section. Diabetic animals with immune injury had an increased number of nuclei (DM, I-, HN: 70 +/- 4; DM, I+, HN: 65 +/- 3) compared with animals with only Heymann nephritis (55 +/- 4) or only diabetes [DM, I-: 52 +/- 4; DM, I+: 54 +/- 3 (mean +/- SE); P less than .05, ANOVA]. An increase in the accumulation of mesangial matrix in diabetic animals with Heymann nephritis was also apparent by light microscopy and immunofluorescence staining of the mesangium for fibronectin. Insulin treatment and control of hyperglycemia did not prevent the development of these changes. Animals with only Heymann nephritis had lesser amounts of immune deposits, which were limited to the subepithelial space and not associated with structural alterations of the mesangium.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1987 Nov
PMID:Accelerated glomerulosclerosis in diabetic rats with immune complex injury. 331 53

The transport of sugars in the isolated small intestine of diabetic rats was examined. It was found earlier (Csaky and Fischer 1981 and 1984) that one symptom of the diabetes, hyperglycemia, sustained for at least 4 hours, causes a marked enhancement of the mucosal-to-serosal flux of glucose, galactose and 3-0-methylglucose. Based on the finding that the enhanced sugar flux was inhibited by phloretin but not by phlorizin and was completely abolished by the protein-synthesis inhibitor, cycloheximide, the theory was proposed that sustained maintenance of high blood sugar induces the synthesis of new sugar carrier sites which are mostly likely localized in the basolateral membrane. In the present study it was found that sustained hyperglycemia significantly enhances the mucosal-to-serosal flux of 2-deoxy-glucose (2DG) but does not alter the flux of alpha-methylglucoside (alpha MG). As it is known that in the small intestine alpha MG is preferentially transported in the brush border while 2DG is a preferred substrate for the basolateral membrane, the present findings corroborate the theory that the enhancement of the intestinal sugar transport produced by sustained hyperglycemia is localized in the basolateral membrane. A working hypothesis is proposed that the high blood sugar sensing receptor localized in the basolateral membrane is identical with the transport receptor (carrier).
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PMID:Membrane-transport of sugars in diabetes mellitus. 338 Aug 23

The substrate specificities of calcium/phospholipid-dependent kinase-C (PKC) were examined in rat kidney cortex, and localization of the protein was studied after the induction of diabetes. The cytosolic kinase was eluted from an anion exchange resin using a linear gradient of 0-0.15 M NaCl. A sharp peak of activity was demonstrated at approximately 80 mM using histone as a substrate. The kinase demonstrated a broad pH optimum of 6.5-8.0. ATP was the preferred phosphorus donor. The Ka for ATP averaged 2.6 +/- 0.1 microM (n = 4) and was not different in diabetic animals. Lysine-rich histones, but not arginine-rich or mixed histones, were the most suitable phosphorus acceptors. Phosphatidylserine stimulated kinase activity with Ka of 4.5 +/- 0.7 microM in the presence of 20 microM diolein (n = 3). Twenty micromolar diolein in the presence of 25 microM phosphatidylserine lowered the apparent Ka for calcium from 17.2 +/- 1.4 to 3.3 +/- 1.5 microM (n = 3; P less than 0.01). Similar data were evident in diabetic animals. Diabetic renal growth was induced by the injection of streptozotocin (35 mg/kg, iv). At the end of 4 weeks, blood glucose averaged 119.6 +/- 7.4 mg/dl in vehicle-injected controls and 548.7 +/- 21.6 mg/dl in diabetic animals (n = 5; P less than 0.001). Despite reduced weight gains in diabetic animals, renal protein content was increased in this group compared to the control value. Neither cytosolic nor proximal tubule basolateral membrane PKC activity changed after the induction of diabetes; however, luminal brush border PKC activity increased from 83.8 +/- 4.6 pmol/mg.min in control animals to 107.3 +/- 55 pmol/mg.min in diabetic animals (n = 5; P less than 0.02). The increased activity in the brush border membrane may have important consequences for the growth response of the kidney in diabetes.
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PMID:Characterization and localization of calcium/phospholipid-dependent protein kinase-C during diabetic renal growth. 340 97

Previous studies have demonstrated enhanced active and passive uptake of many nutrients in animals with experimental diabetes. These changes in absorption cannot be explained by differences in intestinal morphology, although the brush border membrane (BBM) phospholipids do change in diabetes. Manipulation of diet produces alterations in intestinal uptake of lipids and glucose. This study was undertaken to determine the effect of diet and diabetes on jejunal morphology and BBM lipid composition. Rats were rendered hyperglycemic with streptozotocin and were fed for 2 weeks on a diet that was high or low in carbohydrate, essential fatty acids, cholesterol, or protein. In both control and diabetic rats, these diets produced changes in villus height and BBM sucrase and alkaline phosphatase activities. In both control and diabetic rats, BBM phospholipids were unaffected by changes in the dietary content of essential fatty acids, cholesterol, or protein, but total BBM phospholipid content was reduced in animals fed low as compared with high carbohydrate diet. Total BBM phospholipid content was higher in diabetic than in control animals fed the low protein diet, whereas BBM phospholipid content was lower in diabetic than in control animals fed the high carbohydrate diet, and was even lower in diabetic animals fed the low as compared with the high carbohydrate diet. These changes in total phospholipids were due to alterations in the BBM content of phospholipids containing choline. In control animals, BBM cholesterol was higher in rats fed the low as compared with the high cholesterol diet, or the low as compared with the high protein diet.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Diets alter jejunal morphology and brush border membrane composition in streptozotocin-diabetic rats. 356 35

In early stages of permanent renal injury or extensive ablation, structural and functional adaptations associated with hypertrophy partially compensate for nephron losses. Glomerulotubular balance is maintained in these conditioned nephrons by intrinsic tubule and peritubular capillary adaptations that parallel single nephron glomerular filtration rate (SNGFR). Studies of Na+-H+ exchange in renal cortical brush border membrane vesicles indicate that tubule functional adaptation is not tied to loss of renal mass per se but rather to factors such as dietary protein content that set the level of SNGFR. Likewise, the structural heterogeneity that follows chronic renal injury or extreme ablation of renal mass is less a consequence of nephron injury than of adaptation linked to dietary protein intake. Indeed, since dietary protein restriction blunts the need for compensatory glomerular hyperfiltration, there is neither a stimulus for nephron hypertrophy nor for enhanced tubule ion and fluid transport. In rats with remnant kidneys, experimentally induced diabetes mellitus, or severe hypertension, increases in glomerular pressures and flows precede proteinuria, glomerular sclerosis, and azotemia. Protein restriction prevents these hemodynamic adaptations as well as the late complications. Similar conclusions appear to be applicable to a wide spectrum of clinical circumstances characterized by reduced nephron number.
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PMID:Nephron adaptation to renal injury or ablation. 389 71

We examined the hypothesis that the decreased renal accumulation of aminoglycosides in rats with streptozotocin-induced diabetes mellitus is due to decreased membrane binding of drug consequent to reduced membrane content of the putative aminoglycoside receptor, phosphatidylinositol. Renal brush border membrane (BBM) and basolateral membrane (BLM) vesicles were prepared from normal and diabetic Sprague-Dawley rats by differential centrifugation and Percoll gradient techniques which yielded relatively pure membrane fractions as assessed by measurements of marker enzymes and by electron microscopy. Binding of [3H]netilmicin to plasma membranes was performed using a fast filtration technique. Scatchard analysis of the binding data indicated that netilmicin bound to a single class of receptors on BBM and BLM from normal rats with an affinity constant of 33 +/- 2 X 10(3)M-1 and 23 +/- 2 X 10(3)M-1, respectively. The maximal binding capacity of BLM (70 +/- 4 nmol/mg of protein) was significantly greater (P less than .01) than that of BBM (38 +/- 1 nmol/mg of protein). The affinity constants and maximal binding capacities of BBM and BLM from diabetic rats were not significantly different from those of normal rats. Moreover, 2 days of gentamicin injections at 100 mg/kg/day for 2 days had no appreciable effect on these binding parameters in either group. In control rats the total phospholipid content of BLM (785 +/- 19 nmol/mg of protein) was significantly greater (P less than .01) than that of BBM (592 +/- 19 nmol/mg of protein) and reflected significantly greater quantities of sphingomyelin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and phosphatidylinositol.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[3H]netilmicin binding constants and phospholipid composition of renal plasma membranes of normal and diabetic rats. 399 20


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