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

Cell fractionation, enzyme analysis, and electron microscopy were used to study the effects of streptozotocin-induced diabetes and insulin replacement on liver structure and function. In liver homogenates from diabetic rats, glucose-6-phosphatase (G-6-Pase) activity was stimulated about 2 1/2-fold over that found in normal animals. Analyses of isolated rough and smooth microsomes from diabetic rats for G-6-Pase activity showed a fourfold increase in the smooth microsomes and a small increase in enzyme activity in rough microsomes when compared with these fractions from control animals. Associated with the increased enzyme activity was a reduction in liver glycogen. Insulin treatment of the diabetic rats caused a fall in homogenate G-6-Pase levels to approximately normal values and stimulated the accumulation of hepatic glycogen. Administration of insulin to these animals also caused a decrease in G-6-Pase activity, which was most pronounced in the smooth microsomes. Studies with the electron microscope revealed ultrastructural alterations in livers of the diabetic rats, which were most striking in the periportal region of the lobule. Periportal hepatocytes from diabetic rats displayed dispersed particles of glycogen separated by cytoplasm rich in SER rather than dense masses of glycogen with little SER, as is characteristic of these cells in normal animals. Centrilobular cells from the diabetic animals displayed some disorganization of the RER and a dispersed pattern of glycogen with abundant SER, similar to the pattern found in these cells from normal animals. After insulin treatment the periportal cells appeared normal morphologically, whereas the centrilobular hepatocytes displayed regions of both dense masses and dispersed glycogen. In the glycogen masses, little SER was found; however, in the areas of dispersed glycogen particles, an abundance of this organelle was evident. We conclude from these studies that diabetes causes an increase in amount of hepatic smooth endoplasmic reticulum (SER), especially within periportal hepatocytes. The results of cell fractionation indicate that membranes of the smooth endoplasmic reticulum are enriched in G-6-pase. We interpret these results to indicate that diabetes causes hepatocytes to form additional smooth endoplasmic reticulum with specialized membranes, at least with respect to G-6-Pase. It is suggested that this cellular specialization is a response of the hepatocyte to the diabetic state, namely, a demand for increased hepatic glucose production and release into the blood stream, thus contributing to the hyperglycemia characteristic of this disease. Insulin administration to the diabetic animals reverses the above alterations.
Diabetes 1979 Jul
PMID:Hepatic glucose-6-phosphatase activities and correlated ultrastructural alterations in hepatocytes of diabetic rats. 22 Dec 99

To gain information on the manner in which insulin suppresses lipolysis in man, isolated adipocytes, prepared from subcutaneous adipose tissue, were incubated with insulin (100 microunits/ml) alone and in combination with isoproterenol (10(-7) M or 10(-8) M). Cyclic AMP concentration was measured at 60 min; glycerol release, used as an index of lipolysis, was determined at 45 and 75 min. Insulin consistently reduced both basal and stimulated cyclic AMP and glycerol release: the degree of suppression of each was comparable. In subsequent experiments, the ability of insulin to suppress glycerol release stimulated by isoproterenol, theophylline, and dibutyryl cyclic AMP (dbcAMP), respectively, was compared. Insulin substantially reduced the raised levels of cyclic AMP and glycerol release prompted by isoproterenol and theophylline, but it had little effect on increases caused by dbcAMP. These findings support the view that reduction in cyclic AMP is an important component in the regulation of fat mobilization by insulin.
Diabetes 1979 Nov
PMID:Insulin inhibition of lipolysis of human adipocytes: the role of cyclic adenosine monophosphate. 22 42

The association of chronic pancreatitis with diabetes is not very common. Men are the usual victims and ethylism the usual cause. The most common age of onset is between 40 and 50. Insulin treatment is much more frequent than for idiopathic diabetics. Diabetic heredity is probable. Calcifying pancreatitis is the most frequent form. Micro and macroangiopathic complications are found. A statistical comparative study with a matched series of idiopathic diabetics reveals no difference in the onset of vascular complications. The rate of triglycerides is statistically lower in pancreatitis (p less than 0.001). The other biological rates are the same (cholesterol, uricemy, alpha 2 macroglobulin). Diabetic stability is no more difficult to obtain than for idiopathic diabetics. In most cases the diet should be wide and alcohol must be prohibited.
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PMID:[Diabetes and chronic pancreatitis. Report of twenty cases (author's transl)]. 23 6

In animal tissues the pyruvate dehydrogenase complex is regulated by product inhibition and by a phosphorylation-dephosphorylation cycle catalysed by a kinase and a phosphatase. Physiologic and molecular aspects of this regulation are reviewed, and the results of recent studies are described. Insulin deficiency in the rat (diabetes or starvation) is shown to inhibit the conversion of inactive (phospho-) complex into active (dephospho-) complex by the phosphatase by an effect on the substrate for the phosphatase (phosphorylated complex). This change is stable and persists during isolation, incubation, and extraction of mitochondria or purification of phosphorylated complex. The subunit ratios in the purified pig heart pyruvate dehydrogenase complex and the stoichiometry of phosphorylations have been determined by radioamidination and incorporation of 32P. The ratios of decarboxylase tetramer (alpha 2, beta 2) : dihydrolipoyl acetyltransferase monomer : dihydrolipoly dehydrogenase monomer were 1:1:0.5. Inactivation of the complex was accomplished by incorporation of a single phosphate into one alpha subunit of the decarboxylase tetramer. Two further phosphates are then incorporated and these additional phosphorylations inhibit reactivation of the complex by the phosphate. It is suggested that multisite phosphorylations may inhibit reactivation of the complex by the phosphatase in diabetes and in starvation.
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PMID:Regulation of pyruvate dehydrogenase by insulin action. 23 84

In view of the importance of insulin in hepatic cell proliferation and regeneration, disturbances might be expected in these processes in diabetics. The relative importnace of insulin replacement given intraportally rather than subcutaneously is discussed. Results are presented showing that even when normoglycaemia is achieved with peripheral insulin infusion using the 'artificial pancreas' there are still abnormalities in intermediary metabolism. The incidence of cirrhosis in diabetes is reviewed and it is concluded that the evidence is poor for an increase in diabetics. Finally it is shown that in the normal diabetic rat changes are observed after partial hepatectomy consistent with an increase in redox potential within the regenerating liver. Insulin treatment improves redox status but does not completely reverse the changes shown.
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PMID:Hepatotrophic factors: implications for diabetes mellitus. 24 6

Glucose utilization and the conversion of glucose to lactate, CO2, glycogen and lipids are decreased in the aorta from diabetic rats and rabbits. In addition the incorporation of amino acid into protein is reduced in diabetic rat aorta. The metabolic changes produced by diabetes are counteracted by insulin treatment, but there is a time lag of about 2 days before the effect of insulin treatment appears. The membrane transport of glucose in smooth muscle is carried out by a specific transport system of the facilitated diffusion type. A rate limiting influence of membrane transport on glucose metabolism is found in bovine mesenteric arteries and rabbit colon smooth muscle. In these preparations the influence of glucose concentrations on glucose metabolism is most pronounced in the range 0-11.1 mmol exhibiting saturation at higher glucose concentrations. Insulin in a high concentration (0.1 U/ml) has acute (less than or equal to 3 h) metabolic effects in vitro on smooth muscle which are qualitatively similar to those in skeletal muscle, but are weaker and appear later. The threshold concentration for the acute metabolic effects of insulin on smooth muscle in vitro is 10-100 times above the physiological levels, indicating a low acute sensitivity to insulin.
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PMID:Influence of diabetes on metabolism of vascular smooth muscle. 27 64

There is an increasing evidence that autoimmune mechanisms may have a role in the pathogenesis in insulin-dependent diabetics. The numerical and functional study of peripheral blood lymphocytes in diabetes mellitus might indirectly contribute to the understanding of its pathogenesis. In this study, detection of peripheral blood T lymphocytes was measured by rosettes with sheep red blood cells (SRBC), and B lymphocytes were measured by immunofluorescence with specific antiserum to immunoglobulins. The mean (+/- SD) percentage of SRBC was 67.6 +/- 7.2 in 21 normal subjects, 71.5 +/- 7.0 in 15 insulin-dependent diabetics, and 68.6 +/- 6.7 in 30 insulin-independent diabetics. There was no difference in the absolute T-lymphocyte number per mm3 in these three groups. Insulin-dependent diabetics showed a normal percentage and absolute number of B lymphocytes when compared with normal subjects.
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PMID:[Subpopulations of peripheral lymphocytes in insulin-dependent diabetics (author's transl)]. 30 69

Cell-mediated immunity was evaluated in patients with diabetes mellitus by delayed hypersensitivity skin tests and in vitro lymphocyte transformations. Only 44% of diabetic patients had skin test reactivity to Candida antigen, compared with 88% of normal controls (P < 0.001). Insulin-dependent diabetic (IDD) patients had abnormally low lymphocyte transformation responses to phytohemagglutinin, concanavalin A, and streptokinase-streptodornase (P < 0.05). This defect was not corrected by culturing the cells in nondiabetic plasma. IDD patients with persistent hyperglycemia (fasting serum glucose level, >200 mg/dl) had lower levels of transformation than did IDD patients with fasting serum glucose levels less than 150 mg/dl. Lymphocytes from two IDD patients with poor lymphocyte transformation responses had marked improvement in response to phytohemagglutinin when the lymphocytes were cultured after a preincubation period designed to deplete cultures of suppressor activity. Seven IDD patients were studied serially over 12 months. Lymphocyte transformation responses in four of these patients improved coincidentally with a change in the level of fasting hyperglycemia from >200 to <150 mg/dl. The other three IDD patients with consistent fasting serum glucose levels of >200 mg/dl had poor lymphocyte transformation responses. Diabetic patients have demonstrable defects in lymphocyte function which improved in a small number of patients with reduction in the level of fasting hyperglycemia.
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PMID:Cell-mediated immunity in diabetes mellitus. 30 93

Insulin content was studied by radioimmunological and histochemical methods in the erythrocytes and the blood serum of patients with acromegaly and the postpartum panhypopituitrism (Sheehan's syndrome) in comparison with that in healthy persons on fasting stomach and after glucose-tolerance test (GTT). It appeared that the erythrocytes of healthy persons contained 50 times more insulin on fasting stomach than the blood serum. In persons with acromegaly complicated by diabetes mellitus insulin content in the blood serum was almost double that in healthy individuals. But this "hyperinsulinism" was only seeming, since the hormone reserves in the organism (erythrocyte insulin content) were sharply diminished. Sheehan's syndrome was characterized by hypoinsulinemia (both in the serum and in the erythrocytes). After the GTT the insulin content rose in the serum, and decreased in the erythrocytes. This indicated that erythrocytes participated in the homeostasis regulation of glycemia.
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PMID:[Insulin content in the erythrocytes and blood serum of patients with acromegaly and Sheehan's syndrome]. 32 22

In order to clarify the physiologic role of somatostatin in insulin release, rat pancreatic islets treated by somatostatin antiserum were incubated in media containing various concentrations of glucose. Insulin release from antiserum-treated islets was significantly elevated above that from nontreated ones at 3.3 and 8.3 mM glucose, while the former was not different from the latter at 16.7 mM glucose. It is suggested that somatostatin plays an important role in the regulation of insulin release in the physiologic range of glucose concentration.
Diabetes 1977 Jul
PMID:Physiologic role of somatostatin. Insulin release from rat islets treated by somatostatin antiserum. 32 6


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