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

The clinical features of the experimental hyperosmolar diabetic (EHD) rat model resemble those seen in the human syndrome--extreme hyperglycemia without ketoacidosis is common to both. The absence of ketoacidosis in the syndrome has been ascribed to both substrate (free fatty acid) deficiency and to interference with hepatic ketone body synthesis. The potential for hepatic ketone body synthesis in the experimental model has been directly assessed by challenging the EHD animals with medium-chain triglycerides (MCT) administered intragastrically. This neutral lipid, largely consisting of C8 and C10 fatty acids, leads to a dose- and thime-related increase in the plasma concentration of acetoacetate and beta-hydroxybutyrate. The EHD rats respond to MCT with an increase in plasma ketone bodies that rises to levels that are twice as high as those observed in normal rats receiving MCT and are equivalent to the levels seen in untreated ketoacidotic animals. These data indicate that hepatic medium-chain fatty acid oxidation and ketogenesis are unimparied in the EHD animal. An analysis of the factors responsible for the greater ketogenic response in the EHD rat reveals that moderate diabetes and dehydration enhance MCT-induced ketone body accumulation, while cortisol is without effect. The plasma free fatty acid concentration in EHD animals does not differ from normal rats, but is significantly lower than that seen in diabetic ketoacidosis. These data support the concept that a principal reason for the absence of ketoacidosis in the EHD syndrome is the limitation in availiability of substrate, free fatty acids, for ketone body synthesis.
Diabetes 1975 Mar
PMID:Experimental hyperosmolar diabetic syndrome. Ketogenic response to medium-chain triglycerides. 12 10

Using [14-C]lysine protocollagen substrate prepared from chick embryo tibiae, lysyl hydroxylase activity was found in the 17 000 times g supernatant and particulate fractions obtained from homogenates of isolated rat renal glomeruli. Specific activities using the latter as an enzyme source were about 20-30% that of the supernatant. [14-C]Hydroxylysine formation was proportional to substrate and enzyme concentration, and to time for up to 120 min of incubation. Omission of alpha-ketoglutarate and ascorbate in the incubational assay markedly depressed activity. Hydroxylation of substrate by supernatant enzyme from streptozotocin diabetic rats was significantly increased over that of normal. In contrast, the activity of supernatant fractions from glomeruli of pancreatectomized, normoglycemic animals did not differ from that of non-operated controls. It is concluded that elevated glomerular lysine hydroxylase activity accompanies the increased glomerular collagen synthesis found in streptozotocin diabetes, and that chronic hyperglycemia may be implicated in these changes.
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PMID:Glomerular protocollagen lysyl-hydroxylase activity in streptozotocin diabetes. 12 80

The factors influencing the development of impaired sciatic motor nerve conduction velocity (MNCV) in acute experimental diabetes were examined. Decreased MNCV developed by the 14th day after streptozotocin administration but only in rats which became hyperglycemic. Insulin treatment, begun on day 3, failed to prevent imparied MNCV in diabetic rats in which improved or normal weight gain and a decreased degree of hyperglycemia was induced. However, insulin treatment prevented the development of impaired MNCV in a group of diabetic rats in which the tail vein plasma glucose concentration was never found to exceed 160 mg/dl during days 6 through 14, andin which the mean plus or minus SEM of the average plasma glucose concentration for each animal during the same period was 75 plus or minus 18 mg/dl. In normal rats fed diets containing 0.011% or 0.069% free myoinositol (a presumably normal range), sciatic nerve free myoinositol concentrations were 90- and 60-fold higher than those in plasma. On these diets the development of impaired MNCV in the diabetics was associated with a decrease in nerve free myoinositol as compared with nerves from normals fed the same diet, despite similar plasma levels in the normals and diabetics. Plasma and nerve free myoinositol increased with increasing dietary myoinositol content in both normals and diabetics, and nerve myoinositol content could be acutely increased by an i.p. myoinositol load. By supplementing the diets with 1.0% myoinositol, the difference in nerve myoinositol in normal and diabetic rats on day 14 was abolished; on this diet the development of impaired MNCV in the diabetics was moderated or totally prevented, despite persistent hyperglycemia and elevated nerve sorbitol and fructose concentrations. Insulin treatment that prevented impaired MNCV prevented a decrease in nerve myoinositol in diabetics. These studies suggest that insulin deficiency, and possibly hyperglycemia, are primary factors in the development of imparied MNCV in acute experimental diabetes. However, the development of impaired MNCV appears to be related in some manner to a derangement in the regulation of nerve free myoinositol content, which appears to be subject to modification by increases in plasma myoinositol concentration over a critical range.
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PMID:Effects of insulin and dietary myoinositol on impaired peripheral motor nerve conduction velocity in acute streptozotocin diabetes. 12 20

The minor hemoglobins AIa, AIb, and AIc were studied in mice with either genetic or chemically induced diabetes. Hemoglobin AIc was elevated approximately twofold in all the phenotypically diabetic mice studied (C57BL/KsJ-db/db, C57BL/KsJ-ob/ob, C57BL/6J-db/db, and alloxan- and streptozotocin-treated mice). Elevation of the hemoglobin AIc in C57BL/6J-db/db mice was of short duration, reflecting the transitory diabetes characteristic of these mice. The degree of increase of hemoglobin AIc levels was unrelated to severity of hyperglycemia, duration of diabetes, age of mouse, or body weight. It is not known what factor(s) dictates the steady-state concentration of hemoglobin AIc.
Diabetes 1976 Jan
PMID:Increased hemoglobin AIc in diabetic mice. 12 80

In order to study the nephropathy associated with experimental streptozotocin diabetes, serila morphologic, ultrastructural, immunohistologic, and functional studies were done in diabetic Lewis rats to study the course of the nephropathy. Early in the course of diabetes, these animals developed an increase in mesangial matrix, with electron-dense material, IgG, and C3 in the mesangium. These alterations were progressive. Mesangial bars, proximal tubular vacuolization, and myeloid bodies were also present. Progressive increase in protein excretion and increase in creatinine clearance were observed. Hyperglycemia was accompanied by weight loss, persistent glycosuris, hyperphosphaturia, and hypercalcuria. Urinary glomerular basement membrane-like protein and major urinary protein were decreased. Normal age-matched controls showed no abnormalities. Some of the changes observed in diabetic rats are present in human diabetes.
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PMID:The kidney in streptozotocin diabetic rats. Morphologic, ultrastructural, and function studies. 13 91

These investigations delineate the recently described suppression of a form of cellular hypersensitivity in mice with streptozotocin-induced diabetes mellitus using a variety of cell-mediated immunologic responses in animals with several different forms of diabetes. Streptozotocin- and alloxan-induced diabetic mice and db/db genetically determined diabetic mice showed reductions in the areas of inflammation around Schistosoma mansoni eggs injected into the pulmonary vasculature of 68, 70, 77%, respectively. In contrast, streptozotocin-induced diabetes had no effect on the nonimmunologic foreign body granuloma around divinyl benzene copolymer beads injected into the pulmonary arterioles. Animals protected from diabetes by treatment with nicotinamide before streptozotocin administration did not develop hyperglycemia and had normal areas of immunologic granuloma formation around schistosome eggs. Treatment with insulin reversed the suppression of schistosome egg granuloma formation in both streptozotocin- and alloxan-diabetic animals. Two additional in vivo parameters of cellular immunologic reactivity were examined in streptozotocin-induced diabetes: delayed footpad swelling was essentially eliminated; skin graft survival across the H-2 area was significantly prolonged from 10.2 days in the controls to 14.4 days in moderately diabetic A/J mice. These observations suggest that diabetes mellitus is associated with suppression of cell-mediated reactions in vivo and that the defect is reversible with insulin treatment.
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PMID:Induced and spontaneous diabetes mellitus and suppression of cell-mediated immunologic responses. Granuloma formation, delayed dermal reactivity and allograft rejection. 13 Mar 84

Six non-nitrosated and three nitrosated analogs of the antitumor and diabetogenic agent, streptozotocin, have been found to produce hyperglycemia in fasted rats. The hyperglycemia produced by the non-nitrostaed analogs was of early onset and did not result in the production of permanent diabetes. The data emphasizes the important role of the nitroso group of streptozotocin in the production of the hypoglycemic and permanent diabetic phases while the sugar moiety may have a direct influence on production of the early hyperglycemia phase.
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PMID:Hyperglycemic activity of some non-nitrosated streptozotocin analogs. 13 66

Multiple small injections of streptozotocin produce a delayed, progressive increase in plasma glucose in mice within 5-6 days after the injections, in association with pronounced insulitis and induction of type C viruses within beta cells. Multiple subdiabetogenic doses of streptozotocin in rats and multiple injections of another beta cell toxin, alloxan, in mice did not induce insulitis although hyperglycemia followed the injection of larger quantities of both agents. In mice, the prior injection of 3-O-methyl-D-glucose (3-OMG) or nicotinamide attenuated the diabetic syndrome produced by streptozotocin; however, 3-OMG was more protective. Rabbit antimouse lymphocyte serum, alone, provided partial protection but, when given together with either 3-OMG or nicotinamide, effectively prevented the streptozotocin-induced diabetic syndrome. Cessation of these preventive treatments was followed by the appearance of insulitis and diabetes. These findings suggest that multiple injections of streptozotocin induce, in susceptible hosts, the triad of direct beta cell cytotoxicity, virus induction within beta cells, and cell-mediated autoimmune reaction. These factors, acting separately or in concert, appear to induce a destructive insulitis and severe diabetes. The relative importance of each component and the factors governing host susceptibility remain to be clarified.
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PMID:Studies of streptozotocin-induced insulitis and diabetes. 14 53

Multiple injections of subdiabetogenic doses of streptozotocin (SZ) to CD-1 male mice produce a diabetic syndrome that includes a cell-mediated immune reaction against the pancreatic islet. The importance of the host genetic background in the pathogenesis of this model of diabetes was studied by comparing various inbred strains of mice. Of eight strains of mice studied, only C57BL/KsJ developed insulitis and hyperglycemia comparable to that observed in CD-1 mice. In two mouse strains (DBA/J and BALB/cJ) having an H-2d haplotype similar to the C57BL/KsJ, only mild insulitis and glucose intolerance were observed. These data suggest that major histocompatibility complex genes, as presently defined, cannot be the only determinant of the severity of hyperglycemia and insulitis in this model.
Diabetes 1977 Oct
PMID:Genetic influence of the streptozotocin-induced insulitis and hyperglycemia. 14 86

Hyperglycemia induced in animals by beta cell toxins or by pancreatectomy can be reversed by pancreatic islet transplantation. Abnormal carbohydrate metabolism in juvenile onset human diabetics has also been corrected, albeit temporarily because of graft rejection, by pancreatic transplantation. It does not necessarily follow that naturally occurring diabetes in animals or adult onset diabetes in man would respond to similar treatment. Islet transplantation was studied in mice with chemically induced or genetically determined diabetes. Streptozotocin-induced diabetic mice were permanently cured by syngeneic islets and, when immunosuppressed, were rendered normoglycemic for six weeks after receiving xenogeneic rat islets. In contrast, histocompatible islets from normoglycemic coisogenic donors were ineffective in hyperglycemic db/db recipients as were xenogeneic rat islets in immunosuppressed db/db hosts. However, when islets were isolated from db/db donors and transplated to genetically normal coisogenic mice, which had been rendered hyperglycemic with streptozotocin, they became normoglycemic. Apparently the metabolic defect in the db/db mice, which is similar in some ways to human maturity onset diabetes, does not reside in their islets as these cells can function normally if transplanted to genetically nondiabetic hosts. In two other types of genetic diabetes (ob/ob and NZO) islet transplantation was more effective. Pancreatic transplantation is unlikely to be the proper treatment for all types of diabetes even if technical and immunological problems are overcome.
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PMID:Islet transplantation in genetically determined diabetes. 14 16


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