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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The fatty acid composition of phospholipids and triglycerides in heart muscle was examined in normal and alloxan-diabetic male Wistar rats. In diabetes the major phospholipids, phosphatidyl choline and phosphatidyl ethanolamine, showed significant changes in fatty acid composition, whereas cardiolipin and phosphatidyl serine + phosphatidyl inositol did not show marked changes in fatty acid profile. In phosphatidyl choline there was a significant diminution in arachidonic acid, 20 : 4(n-6) and palmitic acid, 16 : 0, and a corresponding increase in linoleic acid, 18 : 2(n-6), and stearic acid, 18 : 0. In phosphatidyl ethanolamine the level of 20 : 4(n-6) was significantly reduced. The diabetic heart had normal levels of individual phospholipids, whereas the triglycerides were increased by 90% and contained significantly higher levels of 18 : 2(n-6). The results confirm that diabetes is associated with a diminution in fatty acid desaturation, affecting the fatty acid composition of phosphatidyl choline in particular. These changes may be relevant to development of atherosclerosis and relative resistance to catecholamine-induced cardiac necrosis in diabetes.
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PMID:Reduced arachidonic acid levels in major phospholipids of heart muscle in the diabetic rat. 343 62

Plasma amino acid concentrations were measured in six insulin-dependent diabetic women and seven non-diabetic women in early pregnancy while fasting and one hour after a standard meal. Fasting plasma levels of total amino acids and individual amino acids were similar in the two groups, excepting isoleucine, which was raised in the diabetics. One hour post-prandially total amino acid concentrations were similar in the two groups; however, mean concentrations of total branched chain amino acids and mean concentration of the individual amino acids, serine, valine, isoleucine, leucine and tyrosine were elevated in the diabetics. Amino acids are important in early islet development and in insulin secretion from fetal pancreas in vitro. The elevated post-prandial amino acid levels found in pregnant diabetics in early pregnancy may contribute to fetal islet hypertrophy and hyperinsulinaemia.
Diabetes Res Clin Pract 1986 Jun
PMID:Amino acid profiles in early diabetic and non-diabetic pregnancy. 374 58

The influence of diabetes and insulin treatment on the phospholipid content of R3230AC mammary tumors, a hormonally responsive neoplasm, was studied. Diabetes was induced by administration of streptozotocin 3 days prior to tumor implantation. Protamine zinc insulin, 3 IU/rat twice daily, was administered to tumor-bearing rats for 3 days. Enzymatically dissociated tumor cells from diabetic animals showed significant increases in phosphatidyl choline, lysophosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl serine, phosphatidyl inositol, and phosphatidic acid, compared to controls. Diabetic animals treated with insulin displayed reductions in phosphatidyl choline, lysophosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl serine, phosphatidyl inositol, and phosphatidic acid to levels approximating those found in intact (control) animals. However, neither diabetes nor insulin treatment altered sphingomyelin levels. Mammary tumor cells from diabetic animals showed a 21% increase in DNA content compared to that in intact controls and treatment of diabetic animals with insulin lowered DNA level significantly. The responsiveness of both phospholipids and DNA content to changes in the insulin milieu of the host suggest that phospholipids may play an important role in mediating the effects of insulin on growth of R3230AC tumors.
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PMID:Effects of streptozotocin-induced diabetes and insulin on phospholipid content of R3230AC mammary tumor cells. 389 69

The pyruvate dehydrogenase and branched-chain 2-oxoacid dehydrogenase complexes of animal mitochondria are inactivated by phosphorylation of serine residues, and reactivated by dephosphorylation. In addition, phosphorylated branched-chain complex is reactivated, apparently without dephosphorylation, by a protein or protein-associated factor present in liver and kidney mitochondria but not in heart or skeletal muscle mitochondria. Interconversion of the branched-chain complex may adjust the degradation of branched-chain amino acids in different tissues in response to supply. Phosphorylation is inhibited by branched-chain ketoacids, ADP and TPP. The pyruvate dehydrogenase complex is almost totally inactivated (99%) by starvation or diabetes, the kinase reactions being accelerated by products of fatty acid oxidation and by a protein or protein-associated factor induced by starvation or diabetes. There are three sites of phosphorylation, but only sites 1 and 2 are inactivating. Site 1 phosphorylation accounts for 98% of inactivation except during dephosphorylation when its contribution falls to 93%. Sites 2 and 3 are only fully phosphorylated when the complex is fully inactivated (starvation, diabetes). Phosphorylation of sites 2 and 3 inhibits reactivation by phosphatase. The phosphatase reaction is activated by Ca2+ (which may mediate effects of muscle work) and possibly by uncharacterized factors mediating insulin action in adipocytes.
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PMID:Mitochondrial 2-oxoacid dehydrogenase complexes of animal tissues. 613 8

1. Concentrations of polyamines, amino acids, glycogen, nucleic acids and protein, and activities of ornithine decarboxylase and S-adenosylmethionine decarboxylase, were measured in livers from control, streptozotocin-diabetic and insulin-treated diabetic rats. 2. Total DNA per liver and protein per mg of DNA were unaffected by diabetes, whereas RNA per mg of DNA and glycogen per g of liver were decreased. Insulin treatment of diabetic rats induced both hypertrophy and hyperplasia, as indicated by an increase in all four of these constituents to or above control values. 3. Spermidine content was increased in the livers of diabetic rats, despite the decrease in RNA, but it was further increased by insulin treatment. Spermine content was decreased by diabetes, but was unchanged by insulin treatment. Thus the ratio spermidine/spermine in the adult diabetic rat was more typical of that seen in younger rats, whereas insulin treatment resulted in a ratio similar to that seen in rapidly growing tissues. 4. Ornithine decarboxylase activity was variable in the diabetic rat, showing a positive correlation with endogenous ornithine concentrations. This correlation was not seen in control or insulin-treated rats. Insulin caused a significant increase in ornithine decarboxylase activity relative to control or diabetic rats. 5. S-Adenosylmethionine decarboxylase activity was increased approx. 2-fold by diabetes and was not further affected by insulin. 6. Hepatic concentrations of the glucogenic amino acids, alanine, glutamine and glycine were decreased by diabetes. Their concentrations and that of glutamate were increased by injection of insulin. Concentrations of ornithine, proline, leucine, isoleucine and valine were increased in livers of diabetic rats and were decreased by insulin. Diabetes caused a decrease in hepatic concentration of serine, threonine, lysine and histidine. Insulin had no effect on serine, lysine and histidine, but caused a further fall in the concentration of threonine.
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PMID:Polyamine and amino acid content, and activity of polyamine-synthesizing decarboxylases, in liver of streptozotocin-induced diabetic and insulin-treated diabetic rats. 616 56

An alpha-amylase inhibitor isolated from Streptomyces tendae, strain 4158 was re-purified by chromatography on CM- and DEAE-cellulose column. Two inhibitors could be characterized: alpha-amylase inhibitor Hoe-467 A (with aspartic acid as N-terminal residue), and alpha-amylase inhibitor Hoe-467 S (with serine as N-terminal residue). The primary structure was determined by automatic Edman-degradation procedures of the aziranized inhibitor and tryptic peptides, derived from digestions of the performic oxidized, aziranized and maleylated inhibitor, respectively. The alpha-amylase inhibitor Hoe-467 A consists of 74 residues and has a calculated molecular weight of 7958. It is composed of all common amino acids except methionine and phenylalanine. Digestion with pepsin was carried out to determine the disulfide bonds. Two fractions could be isolated, containing one cystine each giving information about the positions of the disulfide bridges. The possible clinical application of the inactivator (diabetes mellitus) is pointed out.
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PMID:[The sequence of the alpha-amylase inhibitor Hoe-467 A (alpha-amylase inactivator Hoe-467 A) from Streptomyces tendae 4158]. 616 65

The biochemistry and ultrastructure of hepatocytes from streptozotocin-diabetic rats adapted to a controlled feeding schedule are described. The microsomal enzyme glucose-6-phosphatase (G-6-Pase), required for glucose release from the hepatocyte was monitored in homogenate preparations at times after the initiation of feeding in rats trained to a 6 h feeding, 18 h fasting cycle. G-6-Pase specific activity which is increased in ad lib fed diabetic rats was not further increased with time after the initiation of feeding in the feeding trained animals. However, the known elevation in G-6-Pase latent activity of the diabetic rat was reduced during the feeding cycle of times of minimum and maximum plasma glucose. Enzyme latency is a reflection of the multicomponent nature of G-6-Pase activity; therefore, plasma glucose levels may influence elements of that multicomponent system. Hepatic rough and smooth endoplasmic reticulum (RER + SER) fractions from the diabetic animals exhibited high and equivalent G-6-Pase specific activities independent of feeding or fasting. Ultrastructural observations of periportal hepatocytes showed a high content of SER correlated with the high G-6-Pase specific activity and closely associated with dispersed particles of glycogen at all times after the initiation of feeding. Also, an increase in SER was observed in the fasted normal animals although particulate glycogen was nearly absent. These findings support earlier work indicating that diabetes stimulates the proliferation of hepatic SER and that the membranes of this organelle are altered from those of the normal animal.
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PMID:Subcellular responses of hepatocytes to diabetes in control-fed rats. 629 20

Both alleles of the insulin gene of a patient with mild diabetes [maturity-onset-diabetes-of-the-young (MODY)-type syndrome] associated with hyperinsulinemia have been cloned, and the sequences have been determined. One allele contained a mutation (single nucleotide transition) in the coding sequence for the B chain at position 24 (TTC leads to TCC), resulting in the loss of a restriction enzyme (Mbo II) cleavage site in the gene. This mutation results in the substitution of serine for phenylalanine in a critically important region of the insulin molecule that is intimately involved in receptor binding. Both insulin alleles were of the alpha type and, aside from a single nucleotide deletion in the 5' region of the normal allele, their sequences were identical to those previously determined.
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PMID:Studies on mutant human insulin genes: identification and sequence analysis of a gene encoding [SerB24]insulin. 631 55

Glucose and gluconeogenic substrates promote the activation of hepatic glycogen synthase in vivo and in vitro; activation occurs as inactive glycogen synthase D is dephosphorylated to active glycogen synthase I by glycogen synthase phosphatase. Impairments of glycogen accumulation and glycogen synthase activation in diabetes have been attributed to decreased glycogen synthase phosphatase activity. To determine the role of glycogen synthase phosphatases associated with cytosol and smooth endoplasmic reticulum in the impairment of glycogen synthase activation, livers of normal and streptozotocin-diabetic fed rats were sampled by freeze-clamping before and after perfusion with a mixture of 25 mM glucose, 10 mM glutamine, 4 mM lactate, and 1 mM pyruvate. Perfusion induced activation of glycogen synthase in normal rats, but activation was reduced in the diabetic rats in proportion to the severity of insulin deficiency (r = 0.72, P less than 0.0001). There was also a close correlation between insulin levels and glycogen synthase phosphatase activities of both cytosol (r = 0.76, P less than 0.0001) and SER (r = 0.71, P less than 0.0001) fractions. In contrast, glycogen phosphorylase phosphatase activity and inactivation of glycogen phosphorylase during perfusion were normal in the diabetic livers. This is the first demonstration that glycogen synthase phosphatase activities in both soluble and SER fractions of liver cells are closely related to circulating insulin levels, and that the impairment of glycogen synthesis in diabetes may result from deficient glycogen synthase phosphatase activity in both cell compartments.
Diabetes 1983 Dec
PMID:Impaired glycogenic substrate activation of glycogen synthase is associated with depressed synthase phosphatase activity in diabetic rat liver. 631 99

The case of a female patient with fasting hypoglycaemia before the development of Type 1 (insulin-dependent) diabetes mellitus is reported. She presented with primary hypothyroidism, partial hypopituitarism, adrenal insufficiency and glucagon deficiency. Thyroid microsomal and gastric parietal cell antibodies were detected as well as HLA-B8, whereas islet cell antibodies were not demonstrable, even 2 years after the onset of diabetes. Plasma chromatography revealed true pancreatic glucagon (IRG3500) close to undetectable in basal samples with a questionable increase from 3 to 18 pg/ml during insulin-induced hypoglycaemia. After an overnight fast, moderate hyperaminoacidaemia was found with elevations of alanine, glycine, serine, arginine and ornithine as seen in pancreatectomized patients. It is suggested that the deficient glucagon secretion in this patient might, at least in part, have been the cause of fasting hypoglycaemia and the failure of glucose recovery following insulin-induced hypoglycaemia. Possible, the A cell deficiency was part of the polyglandular failure syndrome in this patient.
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PMID:Glucagon deficiency associated with hypoglycaemia and the absence of islet cell antibodies in the polyglandular failure syndrome before the onset of insulin-dependent diabetes mellitus: a case report. 635 16


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