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

Experimental diabetes in rats is associated with a degree of hypothyroidism. Hepatic enzymes involved in carbohydrate and lipid metabolism were estimated in control (untreated), control +T3 treated, alloxan diabetic and alloxan diabetic + T3-treated rats. The key glycolytic enzymes, phosphofructokinase and pyruvate kinase, were decreased in activity in diabetes and unchanged by further treatment with T3. In contrast, certain enzymes involve in lipogenesis, ATP-citrate lyase 'malic' enzyme and 6-phosphogluconate dehydrogenase, which were decreased in activity in diabetes, were increased to, or above, control values when diabetic rats were treated with T3. It is suggested that T3 deficiency may play a role in the decrease in enzyme activities observed in experimental diabetes, in particular, some enzymes associated with lipogenesis and the provision of NADPH.
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PMID:Regulation of enzymes of glucose metabolism and lipogenesis in diabetic rat liver by thyroid hormones. 342 30

Sand rats (Psammomys obesus) maintained on a diet providing a free choice between laboratory chow and salt bush (Atriplex halimus) were classified into four groups differing in extent of the diabetic syndrome: A, normoglycemic-normoinsulinemic; B, normoglycemic-hyperinsulinemic; C, hyperglycemic-hyperinsulinemic; or D, hyperglycemic with reduced insulin levels. The metabolic pattern of these groups was characterized by measuring the uptake of fatty acid-labeled, very-low-density lipoprotein-borne triglycerides (VLDL-TG) and [3H]-2-deoxyglucose (2-DOG) into muscle and adipose tissues; incorporation of [14C]alanine into glycogen in vivo; gluconeogenesis from lactate, pyruvate, and alanine in hepatocytes; the effect of insulin on glycogen synthesis from glucose; the oxidation of albumin-bound [1-14C]palmitate and [14C]glucose in strips of soleus muscle; activities of muscle and adipose tissue lipoprotein lipase; and activities of rate-limiting enzymes of glycolysis, gluconeogenesis, and fatty acid synthesis in liver. In group A, uptake of VLDL-TG and activity of lipoprotein lipase were higher in adipose tissue and lower in muscle than in albino rats. In the liver, gluconeogenesis and the activity of phosphoenolpyruvate carboxykinase, as well as lipid synthesis and the activity of NADP-malate dehydrogenase, were higher than in albino rats, whereas activity of pyruvate kinase was lower. In group B, uptake of VLDL-TG by adipose tissue and muscle and lipoprotein lipase activity were similar or higher than in group A. Uptake of 2-DOG by muscle and adipose tissue and activity of liver phosphoenolpyruvate carboxykinase were lower than in group A. In groups C and D, uptake of VLDL-TG and lipoprotein lipase activity in muscle were further increased.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1986 Jun
PMID:Characterization of stages in development of obesity-diabetes syndrome in sand rat (Psammomys obesus). 351 25

The metabolic actions of porcine insulin and biosynthetic human proinsulin on fatty acid and glucose metabolism were studied in rat hepatocytes cultured in monolayer for 24 h. Our aim was to establish whether proinsulin action in the liver is similar to insulin action and whether the relative potencies of the two hormones are the same for different metabolic processes. Proinsulin and insulin exerted a similar maximal inhibitory effect on ketone body formation from palmitate and on gluconeogenesis from pyruvate. The half-maximal effective concentration of proinsulin was 11-13 times that of insulin. The antiketogenic effects of insulin and proinsulin were associated with an increased glycerol 3-phosphate content and a decreased affinity of carnitine palmitoyltransferase for its substrate palmitoyl-CoA. When the basal rate of ketogenesis was increased with isobutyl methylxanthine, the half-maximal effective concentrations of both proinsulin and insulin were decreased, but the relative potency of the two hormones was unchanged. Proinsulin and insulin exerted similar maximal stimulatory effects on glycogen synthesis and on the activities of pyruvate kinase, glucose 6-phosphate dehydrogenase, phosphogluconate dehydrogenase, and malic enzyme. The half-maximal effective concentration of proinsulin was 10-30 times that of insulin. These findings are consistent with receptor binding studies on liver membranes that suggest that proinsulin interacts with insulin-specific and not proinsulin-specific receptors. Our findings also suggest that proinsulin action does not differ from insulin action at a postreceptor site.
Diabetes 1986 Nov
PMID:Regulation of ketogenesis, gluconeogenesis, and glycogen synthesis by insulin and proinsulin in rat hepatocyte monolayer cultures. 353 Aug 57

The pyruvate kinase activity of erythrocytes from normal and diabetic subjects was examined in order to establish this enzyme as a valid indicator of mean cell age in the studies of age-dependent erythrocyte functions. This study reveals that the enzyme activity in the erythrocytes was not affected by the condition of diabetes and suggests that it may provide a simple means for the determination of cell age in erythrocyte insulin binding studies. Present data further indicate that the mean cell age of the erythrocytes from diabetic patients was not significantly different from normal although insulin binding to erythrocytes was markedly reduced when compared with that in the normal subjects.
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PMID:Determination of the mean cell age of erythrocytes from diabetic subjects with pyruvate kinase. 353 76

We studied the effect of spontaneous long-term (9-10 months) diabetes on the heart of Chinese hamsters (CHAD strain) to elucidate the relationship between diabetes mellitus and cardiomyopathy. The diabetic hamsters, aged approximately 11 months, showed body weight loss, hyperglycemia (mean fasting plasma glucose 402 mg/dl), hypoinsulinemia, hyperlipidemia and ketonemia. The diabetic hamsters showed reduced activities of cytoplasmic glycolytic key enzymes; hexokinase, pyruvate kinase and phosphofructokinase, increases in cardiac glycogen and glucose-6-phosphate contents and a 40% decrease in cardiac ATP content, indicating decreased energy production. An accumulation of myocardial triglyceride and cholesterol was found in the diabetic hamsters. In addition, the cardiac norepinephrine content was increased in the diabetic hamsters, suggesting the presence of autonomic nervous disorder. Increased heart weight and thickening of the septum and both ventricular walls were found in the diabetic hamsters. Light-microscopic analysis revealed that 42.9% of the diabetic hamsters had myocardial degeneration without any vascular lesion of extramural large and intramural small vessels, whereas the non-diabetic controls had no myocardial or vascular lesions. These data suggest that the diabetic Chinese hamsters had cardiomyopathy, which is possibly caused by extravascular factors such as metabolic or autonomic nervous disorder although conclusive evidence is lacking.
Diabetes Res Clin Pract
PMID:Metabolic and morphological changes of the heart in Chinese hamsters (CHAD strain) with spontaneous long-term diabetes. 366 31

Phosphoenolpyruvate carboxykinase activity was measured in rat pancreatic islet cytosol and mitochondria. No carboxykinase activity was detected under a variety of conditions, including those that increase phosphoenolpyruvate carboxykinase activity in nonislet tissues, such as starving animals or incubating the islet extracts with Fe2+ or Mn2+ before assaying for enzyme activity. The amounts of islet cytosol protein used exceeded those of liver in companion assays used as controls. It was calculated that if islet phosphoenolpyruvate carboxykinase activity was 0.005 that of liver, or 1 X 10(-5) as high as pyruvate kinase activity in islets, it should have been detected in the assays used. Ferroactivator is a protein that permits Fe2+ to activate phosphoenolpyruvate carboxykinase and it is ubiquitous to many tissues that do and even do not contain the carboxykinase. Ferroactivator activity was not detectable in pancreatic islets. Pyruvate kinase, an enzyme that catalyzes a reaction that is essentially the opposite of that catalyzed by phosphoenolpyruvate carboxykinase (i.e., phosphoenolpyruvate formation), is plentiful in islet cytosol. Therefore, even if phosphoenolpyruvate carboxykinase activity is present in pancreatic islets, it is so low that it is unlikely that phosphoenolpyruvate formation would be favored and the contribution of the carboxykinase to intracellular carbohydrate metabolism must be quantitatively unimportant.
Diabetes 1985 Mar
PMID:Do pancreatic islets contain significant amounts of phosphoenolpyruvate carboxykinase or ferroactivator activity? 388 92

Peripheral hyperinsulinaemia usually found in conventionally treated Type 1 (insulin-dependent) diabetic patients may have deleterious metabolic effects. We have used a hyperinsulinaemic model to examine intermediary metabolism in two key peripheral tissues, aorta and muscle. Nine pigs were immunized with crystalline insulin. Subsequently, they showed an insulin-binding capacity of 86.2 +/- 25.0 pmol/l and fasting total serum insulin of 3.9 +/- 3.1 nmol/l (control range 0.034-0.072 nmol/l), impaired glucose tolerance after oral glucose tolerance testing, significantly elevated levels of peripheral venous serum free insulin and C-peptide, and increased mean post-prandial free insulin/glucose ratios. The immunized pigs showed marked elevation of aorta and muscle triglycerides compared with control pigs (n = 15) but similar levels of non-esterified fatty acids. The glucose-6-phosphate-dehydrogenase, malic enzyme and 3-hydroxyacyl-CoA-dehydrogenase activities were all increased significantly (by 50%-300%) in both aorta and muscle. Phosphofructokinase was decreased in both tissues. Hexokinase was increased in muscle alone whereas pyruvate kinase was significantly decreased in aorta. Glyceraldehyde-3-phosphate dehydrogenase activity was not significantly different in aorta and muscle. Thus in insulin immunized pigs with normal beta-cell function and pronounced peripheral hyperinsulinaemia there was increased peripheral lipogenic activity. These findings have potentially important implications with regard to macrovascular disease in diabetes.
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PMID:Aorta and muscle metabolism in pigs with peripheral hyperinsulinaemia. 388 16

Short-term effects of human proinsulin on metabolic rates and its long-term action on enzyme induction were studied in primary cultures of rat hepatocytes and in the perfused rat liver, and compared with the effects of bovine insulin. In the perfused rat liver, proinsulin decreased the glucagon-dependent increase of glycogenolysis. The action of 0.5 nM glucagon was almost completely suppressed by 100 nM proinsulin. Proinsulin and insulin showed similar potency. In cultured rat hepatocytes, proinsulin stimulated glycolysis up to fivefold with a half-maximal effective dose of 30 nM. Proinsulin induced the key glycolytic enzymes glucokinase and pyruvate kinase by twofold and antagonized the glucagon-dependent induction of phosphoenolpyruvate carboxykinase with a half-maximal effective dose at 3 nM. For the effects in cultured hepatocytes, about 100-fold higher concentrations of proinsulin than of insulin were required.
Diabetes 1985 May
PMID:Insulin-like action of proinsulin on rat liver carbohydrate metabolism in vitro. 388 57

Rabbit pancreatic islet cytosol catalyzes the calcium-activated phosphorylation by [gamma 32P]ATP of a protein with a molecular weight of 57,000 that is precipitated with antipyruvate kinase antibodies. We were unable to demonstrate that phosphorylation in the presence of calcium or cAMP had any immediate effect on rat pancreatic islet pyruvate kinase activity. This finding is consistent with our inability to confirm the finding of others that pancreatic islets contain phosphoenolpyruvate carboxykinase activity (Diabetes, 34:246, 1985). Since the carboxykinase catalyzes phosphoenolpyruvate formation and pyruvate kinase catalyzes essentially the opposite reaction, if the carboxykinase were present in the beta cell, pyruvate kinase would need to be inhibited to prevent recycling of phosphoenolpyruvate.
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PMID:Evidence for phosphorylation of pancreatic islet pyruvate kinase. 389 25

Insulin binding to erythrocytes was shown to lack any relationship to age-related factors of the erythrocyte such as the pyruvate kinase activity and the reticulocyte count in individuals with a normal erythropoiesis. After density separation of the erythrocytes in both normal adults and children and in individuals with increased erythropoiesis, a correlation to age-factors was evident (pyruvate kinase activity/insulin binding r = 0.59, p less than 0.01, reticulocyte count/insulin binding r = 0.44, p less than 0.01). An estimate of the components of variation in the binding showed that the unexplained variance is 60%. In the density separated samples the insulin binding correlated closer to the pyruvate kinase activity than to the number of reticulocytes. During treatment of haematopoietic diseases in the 4 patients with increased erythropoiesis, the disappearance rate for the reticulocyte count was much faster (T 1/2 = 9 days) than that of the insulin binding to erythrocytes (T 1/2 = 37 days) and that of pyruvate kinase activity (T 1/2 = 36 days). In one patient studied after splenectomy, the decrease in insulin binding paralleled the disappearance curve for 51Cr-tagged erythrocytes. These results suggest that insulin binds to erythrocytes, not only during the reticulocyte stage, but throughout their life span, though the binding, which is very closely related to their pyruvate kinase activity, steadily declines as the erythrocytes age.
Diabetes Res 1985 Sep
PMID:The influence of erythrocyte age on estimations of erythrocyte insulin binding in healthy children and adults and in conditions with increased erythropoiesis. 390 88


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