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)

Levels of the G-protein alpha-subunits alpha-Gi-2, alpha-Gi-3 and the 42 kDa, form of alpha-Gs were markedly decreased in hepatocyte membranes from streptozotocin-diabetic animals as compared with normals. In contrast, no detectable changes in alpha-Gi subunits were seen in liver plasma membranes of streptozotocin-diabetic animals, although levels of the 45 kDa form of Gs were increased. G-protein beta subunits in plasma membranes were unaffected by diabetes induction. Analysis of whole-liver RNA indicated that the induction of diabetes had little effect on transcript levels of Gi-3, caused an increase in Gs transcripts and decreased transcript number for Gi-2, albeit to a much lesser extent than was observed upon analysis of hepatocyte RNA. In both hepatocyte and liver plasma membranes, immunoblot analysis showed that levels of the catalytic unit of adenylate cyclase were increased upon induction of diabetes. Under basal conditions, alpha-Gi-2 from hepatocytes of diabetic animals was found to be both phosphorylated to a greater extent than alpha-Gi-2 isolated from hepatocytes of normal animals, and furthermore was resistant to any further phosphorylation upon challenge of hepatocytes with angiotensin, vasopressin or the phorbol ester 12-O-tetradecanoylphorbol 13-acetate. Treatment of isolated plasma membranes from normal, but not diabetic, animals with purified protein kinase C caused the phosphorylation of alpha-Gi-2. Treatment of membranes from diabetic animals with alkaline phosphatase caused the dephosphorylation of alpha-Gi-2 and rendered it susceptible to subsequent phosphorylation with protein kinase C. Low concentrations of the non-hydrolysable GTP analogue guanylyl 5'-imidodiphosphate inhibited adenylate cyclase activity in both hepatocyte and liver plasma membranes from normal, but not diabetic, animals.
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PMID:Diabetes-induced alterations in the expression, functioning and phosphorylation state of the inhibitory guanine nucleotide regulatory protein Gi-2 in hepatocytes. 170 Jul

We investigated by enzyme electrophoresis after prolonged neuraminidase treatment the activity of "intestinal variant" (alpha 2-globulin mobility) alkaline phosphatase (EC 3.1.3.1; ALP) in the plasma of 189 patients selected for disorders (diabetes mellitus, liver cirrhosis, and chronic renal failure) with a known high frequency of increased plasma intestinal (beta-globulin mobility) ALP activity. The overall frequency of the variant ALP was 23.8%, whereas in the samples showing intestinal ALP it was 45.0%. The variant ALP was not observed in the absence of intestinal ALP, nor in patients of blood group A. Its frequency did not differ significantly between the different patient groups. Quantification of the variant ALP by densitometry was unsatisfactory but the quantity could be estimated by subtracting the intestinal ALP activity measured by electrophoresis from the activity determined by immunoassay with monoclonal antibody that reacts with both the intestinal and the variant forms. This indicated median activity of 12 U/L for the variant, approximately equal to that of the concomitant intestinal ALP. From the effects of papain and bromelain treatments, we suggest that "intestinal variant" represents intestinal ALP with attached membrane-binding domain.
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PMID:Intestinal variant alkaline phosphatase in plasma in disease. 170 Jul 41

We previously reported that dog diabetes results in hypercholesterolemia and the accumulation of a high-density lipoprotein (HDL) subclass, HDL1. Hypercholesterolemic diabetic rodents exhibit hyperphagia, intestinal hypertrophy, and increased intestinal cholesterol synthesis and absorption; intestinal 3-hydroxy-3-methylglutaryl (HMG) CoA reductase activity is increased, whereas hepatic activity is unchanged or reduced. To determine whether similar mechanisms operate in the hypercholesterolemic diabetic dog, we measured hepatic and intestinal cholesterologenesis. Streptozocin-alloxan-induced diabetic dogs allowed access to food ad libitum were hyperphagic and hypercholesterolemic (10.1 vs. 4.47 mM) but normotriglyceridemic. Plasma HDL1 concentrations were markedly increased. Differences in renal and hepatic function were not statistically significant, except serum alkaline phosphatase, which was elevated 4-fold (P = 0.0003). Urinary mevalonate, an index of whole-body cholesterol synthesis, was increased 6-fold. Intestinal and hepatic weights were both increased, and direct measurements showed crypt and villus thickening. The activity of HMG CoA reductase per gram organ weight was increased 1.7-fold in liver and 2.1-fold in intestine. Calculated whole-organ activity in intestine was nearly twice that in liver. These observations provide strong evidence that intestinal cholesterogenesis is involved in the pathogenesis of hypercholesterolemia in dog diabetes and support the conclusion that increased cholesterol synthesis plays a role in the hypercholesterolemia of diabetes.
Diabetes 1991 Dec
PMID:Intestinal and hepatic cholesterogenesis in hypercholesterolemic dyslipidemia of experimental diabetes in dogs. 175 3

Variations in the dietary fatty acid composition and cholesterol content are associated with alterations in the intestinal uptake of hexoses and lipids in control and diabetic rats. Changes in the composition of the brush membrane (BBM) lipids may provide a possible mechanism for the observed alterations in transport properties. Accordingly, control and streptozotocin diabetic animals were fed one of four isocaloric semisynthetic diets for two weeks: beef tallow with low cholesterol, beef tallow with high cholesterol, fish oil with low cholesterol or fish oil with high cholesterol. BBM were prepared and assessed for marker enzyme activity and lipid composition. Fish oil feeding was associated with a reduction in total phospholipid content in control and diabetic jejunal and ileal BBM; this fall in total phospholipids was due to a reduction in BBM sphingomyelin. Cholesterol supplementation increased control jejunal BBM sucrase activity in animals fed beef tallow but reduced sucrase activity in animals fed fish oil. In fish oil fed diabetic animals, jejunal and ileal BBM alkaline phosphatase activity was increased with cholesterol supplementation. The elevation in BBM total phospholipids (phosphatidylethanolamine) associated with diabetes in beef tallow fed animals was not observed in the jejunal BBM of animals fed fish oil or in the ileal BBM of animals fed fish oil with high cholesterol. Thus, (a) feeding an omega-3 polyunsaturated fatty acid diet (fish oil) reduced total phospholipid content in BBM of control and diabetic animals, primarily due to a reduction in sphingomyelin; and (b) feeding an omega-3 polyunsaturated fatty acid diet or dietary cholesterol supplementation alter the activity of BBM enzymes. These results suggest that variations in dietary fat composition and the associated changes in BBM composition and enzyme activity contribute to altered intestinal function in diabetes.
Diabetes Res 1991 Mar
PMID:Isocaloric modification of dietary lipids influences intestinal brush border membrane composition in diabetic rats. 180 79

Diabetes and osteoporosis are linked. The question remains, however, as to whether insulin has any direct effect on bone formation. To test this hypothesis we have measured, as a marker of osteoblast activity, alkaline phosphatase (ALP) released by rat limb intact bones incubated in the presence and in the absence of physiological concentration of insulin. The results indicate that insulin significantly (p less than 0.012) increases ALP by a mean value of 48% (from 5.4% to 215%) over matched controls. We conclude that insulin has a direct stimulatory effect on osteoblast activity, and that in the absence of this effect, as in diabetes, bone loss might occur.
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PMID:[Effect of insulin on the activity of bone alkaline phosphatase in culture]. 181 19

The insulin resistance seen in diabetes mellitus has been attributed partly to impaired autophosphorylation of the insulin receptor. It has been suggested that the phosphorylation of serine and/or threonine residues of the insulin receptor may reduce tyrosine autophosphorylation in streptozotocin-induced diabetic rats (STZ-D rats). To elucidate the mechanisms of decreased autophosphorylation of the insulin receptor in diabetic rats, we have investigated the effect of dephosphorylation of the insulin receptor by alkaline phosphatase on the insulin- and protein kinase-stimulating incorporation of 32P into the receptor of the liver from STZ-D rats. Both basal and insulin-stimulated autophosphorylations of the insulin receptor from STZ-D rats were significantly impaired to those from normal rats. Dephosphorylation of the insulin receptor by alkaline phosphatase resulted in an increase in insulin-stimulated autophosphorylation of the insulin receptor from STZ-D rats (43 +/- 13% to 66 +/- 14%, P less than 0.05), but not from normal rats (100% to 109 +/- 12%, NS). Although maximal autophosphorylation of the dephosphorylated insulin receptor was still lower in STZ-D rats than in normal rats, the increase in insulin-stimulated autophosphorylation of the insulin receptor from STZ-D rats by dephosphorylation was higher than that from normal (159.2 +/- 27.2% vs 108.0 +/- 12.4%, p less than 0.01), supporting the idea that the residues of the insulin receptor of STZ-D rats was highly phosphorylated.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes Res 1991 May
PMID:Dephosphorylation of the insulin receptor partially restores the decreased autophosphorylation in streptozotocin induced diabetic rats. 181 77

Islet amyloid polypeptide (IAPP) is the constituent peptide of amyloid in pancreatic islets of Type 2 diabetic patients and in insulinomas. Amyloid formation in Type 2 diabetes is associated with islet cell destruction which may promote formation of autoantibodies to IAPP. An ELISA method has been developed to detect IAPP autoantibodies and used to assay serum from 80 non-diabetic subjects, 49 Type 1 and 228 Type 2 diabetic patients, and 10 patients with insulinomas. Microtitre plates coated with IAPP 1-37 were used to detect antibody binding followed by an alkaline phosphatase conjugated anti-human IgG. ELISA binding decreased with sample dilution and with pre-incubation of the samples with IAPP. The optical density of the substrate reaction was compared with results from a standard serum from a non-diabetic subject (OD ratio). Elevated OD ratios were detected in some subjects from each patient group but the Type 2 diabetic group had significantly higher titres than the non-diabetic subjects (p less than 0.001). The OD ratio was elevated (greater than mean + 2SD non-diabetic group) in 15% of Type 2 and 18% of Type 1 diabetic patients and in 20% with insulinomas. IAPP antibody levels did not correlate with age or gender of subjects, or duration of diabetes. IAPP autoantibodies could be an additional marker for B-cell damage in diabetes.
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PMID:Autoantibodies to islet amyloid polypeptide in diabetes. 183 20

Osteopenia is a recognized complication of diabetes mellitus in humans and experimental animals. We recently found that tetracyclines prevent osteopenia in the streptozotocin-induced diabetic rat and that this effect was associated with a restoration of defective osteoblast morphology (Golub et al., 1990). The present study extends these initial ultrastructural observations by assessing osteoblast function in the untreated and tetracycline-treated diabetic rats. After a 3-week protocol, non-diabetic control and diabetic rats, including those orally administered a tetracycline, minocycline (MC), or a non-antimicrobial tetracycline analog (CMT), were perfusion-fixed with an aldehyde mixture; the humeri were dissected and processed for ultracytochemical localization of alkaline phosphatase (ALPase) and Ca-ATPase activities. Some rats from each experimental group received an intravenous injection of 3H-proline as a radioprecursor of procollagen, and the humeri were processed for light microscopic autoradiography. In addition, the osteoid volume in each experimental group was quantitatively examined by morphometric analysis of electron micrographs. During the diabetic state, active cuboidal osteoblasts in the endosteum of control rats were replaced by flattened bone-lining cells that contained few cytoplasmic organelles for protein synthesis (Golgi-RER system), and active transport (mitochondria). Treating diabetic rats with MC, and even more so with CMT, appeared to "restore" osteoblast structure. During diabetes, bone-lining cells incorporated little 3H-proline or secreted little labeled protein and produced only a very thin osteoid layer. Tetracycline administration to the diabetics increased both the incorporation of 3H-proline by osteoblasts and their secretion of labeled protein toward the osteoid matrix, in a pattern similar to that seen in the non-diabetic controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tetracycline administration restores osteoblast structure and function during experimental diabetes. 183 18

During the period 1950-1985, a total of 179 cases of clinically overt hereditary haemochromatosis (HH) were registered in Denmark, 140 males and 39 females. Median age at diagnosis was 55 years (range 29-81). Diagnostic approaches, symptoms and physical signs at discovery are described. All patients had grade 3-4 liver haemosiderin iron, and cirrhosis was present in 84%. Serum (S-) transaminase was elevated in 92%, S-alkaline phosphatase in 47% and S-bilirubin in 23%, while plasma prothrombin time was below normal in 34%. Females had higher alkaline phosphatase than males (p less than 0.05). Bone marrow haemosiderin iron (n = 81) showed no relation to iron status indicators and was unsuitable as a diagnostic tool. Skin biopsy (n = 56) was positive for haemosiderin iron in 67% and for melanin in 57%, but was of limited value in the assessment of HH. Arthropathy was registered in 44%; arthralgias and clinical joint abnormalities occurred more frequently in females than in males (p less than 0.05). Latent diabetes mellitus was found in 34% and overt diabetes in 55%, being more frequent in males than in females (p less than 0.05). Other endocrine abnormalities were seen in 66%. Cardiac failure was observed in 9% and abnormal ECG in 35%. Males had higher haemoglobin (p less than 0.0001) and S-iron (p less than 0.01) than females, while S-transferrin, transferrin saturation, S-ferritin and mobilizable iron stores showed no significant sex differences. Median transferrin saturation was 87% (range 52-100); values greater than 62% were observed in 96% of the patients. Median S-ferritin was 3,400 micrograms/l (800-12,700) and median iron stores 14.8 g (4.5-36.4).
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PMID:Hereditary haemochromatosis in Denmark 1950-1985. Clinical, biochemical and histological features in 179 patients and 13 preclinical cases. 191 39

The aim of this study was to clarify the clinical significance of urinary enzyme activity in patients with diabetes mellitus. Patients were divided into two groups: group A - 102 outpatients, group B-23 inpatients. Spot urine samples before breakfast from group A and aliquots of 24-hours urine collections at 4 degrees C from group B were used. Urinary enzyme activities (N-acetyl- beta-D-glucosaminidase: NAG, alkaline phosphatase: ALP, leucine aminopeptidase: LAP, gamma-glutamyl transpeptidase: gamma-GTP) were determined by spectrophotometric assay, rate assay, Tuppy method and Orlowski method, respectively. 1) In group A, the percentage of the cases which showed higher than the normal range (NAG: 1.3-8.7, ALP: 4.2-17.7, LAP: 0-22.9 U/g. cer.) was 42.2% in NAG, 21.6% in ALP, and 8.8% in LAP. In a multiple regression analysis, the predictor variables which contributed to NAG were HbA1c, age, urinary protein and the one that contributed to ALP, LAP, gamma-GTP was urinary beta 2-microglobulin. 2) In group B, 87% of NAG was above the normal range (Mean +/- 2 SD; 4.8 +/- 3.9 U/day). There was no difference in the NAG activity between patients with and without nephropathy. The percent of high activities of ALP, LAP and gamma-GTP were 17%, 17%, 4%, respectively. Most of them were patients with nephropathy. There were correlations among ALP, LAP and gamma-GTP, though no correlation existed between NAG and the other three enzymes. These results suggested: 1) NAG reflects lysosomal dysfunction of both glomerular and proximal tubular epithelial cells which may be caused by poor glycemic control.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Clinical significance of urinary enzymes in diabetes mellitus]. 197 16


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