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)

Therapy with enzyme inducing drugs may improve glycemic control in patients with non-insulin-dependent diabetes mellitus. We evaluated the role of a mixed function oxidase system on glucose metabolism with an animal model. Rats were treated with an inducer (phenobarbital), an inhibitor (cimetidine) and a hepatotoxin (carbon tetrachloride) for a week to cause alterations in the liver. The mixed function oxidase system was assayed by determination of the cytochrome P-450 content and NADPH cytochrome c reductase in liver. Carbohydrate metabolism was evaluated by determining blood glucose, enzymes associated with glucose phosphorylation in the liver (glucokinase, hexokinase), glucose storage as glycogen and enzymatic delivery, glucose-6-phosphatase, and peripheral tissue by determining phosphorylating enzyme (hexokinase) and a key glycolytic enzyme (pyruvate kinase) and glycogen content in muscles. The therapy with the inducer enhanced glucose utilization in liver and storage in muscles. The inhibitor decreased the mixed function oxidase system, reduced glucose phosphorylating, but not gluconeogenetic enzymes, in the liver and increased glycolysis in muscles. Carbon tetrachloride, a hepatotoxin, impaired mixed function oxidase, glucose phosphorylating and delivering enzyme activity in liver, reduced blood glucose and caused glycogen accumulation in muscles. The function of liver microsomal enzyme system seems to be closely related to enzymatic glucose metabolism in the liver and muscles.
Diabetes Res 1987 Apr
PMID:Hepatic mixed function oxidase system and enzymatic glucose metabolism in rats. 304 Mar 22

The predictive value of insulin autoantibodies (IAA) was examined prospectively in 58 non-insulin-dependent diabetics (NIDDs) with and without IAA. The longitudinal changes in serum C-peptide (CPR) responses to 100 g oral glucose tolerance tests (OGTTs) as well as IAA and islet cell antibodies (ICA) in these subjects were followed up to 84 mo (mean 38 mo). Based on the positivity for IAA and ICA during the study, the subjects were subdivided into the following four groups; (a) persistently IAA- and ICA-positive subjects (Group 1, n = 7), (b) persistently IAA-negative and ICA-positive subjects (Group 2, n = 18), (c) persistently IAA-positive and ICA-negative subjects (Group 3, n = 3), (d) persistently IAA- and ICA-negative subjects (Group 4, n = 30). In Group 1 subjects serum CPR response to OGTT decreased significantly during the follow-up study (p less than 0.01), while in the remaining three groups, the response did not show any significant change. Blood glucose level during OGTT in Group 1 increased (p less than 0.01), while the values in remaining groups had no significant change. Four out of seven in Group 1 and 3 out of 18 in Group 2 progressed slowly to insulin-dependent state (p less than 0.07 Group 1 vs. Group 2). None of the subjects in Group 3 and Group 4 progressed to insulin-dependent state (p = 0.01 Group 1 vs. Group 4). The percent binding of labeled insulin and titer of ICA did not show any significant change among their positive groups during the study.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes Res 1988 Nov
PMID:Predictive value of insulin autoantibodies for further progression of beta cell dysfunction in non-insulin-dependent diabetics. 307 43

Aldose reductase [aldehyde reductase 2; alditol:NAD(P)+ 1-oxidoreductase, EC 1.1.1.21] catalyzes conversion of glucose to sorbitol. Although its activity is implicated in the progression of ocular and neurological complications of diabetes, the normal function of the enzyme in most cells is unknown. Both aldose reductase activity and substantial levels of sorbitol were previously reported in renal inner medullary cells. In this tissue, the extracellular NaCl concentration normally is high and varies considerably depending on the urine concentration. We report here on a line of renal medullary cells in which medium that is high in NaCl greatly increases both aldose reductase activity and intracellular sorbitol. In these tissue culture cells (and presumably also in the renal inner medulla), the intracellular sorbitol helps balance the osmotic pressure of elevated extracellular NaCl and thus prevents cellular dehydration.
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PMID:Induction of aldose reductase and sorbitol in renal inner medullary cells by elevated extracellular NaCl. 310 2

Preservation of own insulin production (residual pancreatic beta-cell function) has been shown to have a beneficial effect on glycemic control in insulin-dependent diabetic subjects, and its total lack has been suggested to be an independent risk factor during diabetic pregnancy. We studied the influence of residual beta-cell activity on the glucose control and the outcome of pregnancy in 29 diabetic women by sequentially measuring gestational postprandial plasma C-peptide (CPR) levels, diurnal blood glucose curves and blood glycosylated hemoglobin (Hb A1c) and by analyzing the morbidity and mortality of the offsprings. The 9 diabetics with moderate own insulin secretion (CPR levels over 1.0 microgram/l, White classes B and C, later referred to as group I) had significantly better glucose control than the remaining 20 subjects with lower CPR values (White classes C, D and NF, later referred to as group II) (figure 1, table I). There were two intrauterine deaths, both in group II. These deaths (one caused by multiple congenital contracture syndrome and the other by severe intrauterine growth retardation without any evident cause) could not be straightly connected with diabetes. Respiratory distress syndrome was seen in group II only. There was no other significant difference in the neonatal morbidity between the two groups (table II). All mothers of RDS infants were in White class NF where the birthweight was also smaller than in classes B and C. These were the only differences in neonatal morbidity between the White classes (table III). In conclusion, moderate residual beta-cell function seemed to be clinically important in maintaining strict glucose control during gestation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Maternal residual beta-cell function and the outcome of diabetic pregnancy. 329 78

A case of diabetes mellitus who had high levels of fasting immunoreactive insulin (IRI) and low levels of immunoreactive C-peptide (CPR) is reported. Examination of her serum disclosed the presence of IgG class k + lambda type anti-insulin autoantibodies. She has never been treated with insulin, nor had drugs which have been reported to be responsible for inducing insulin autoimmune syndrome. Despite the presence of autoantibodies against insulin, she has never experienced hypoglycemia. Significance of the production of autoantibodies against insulin and physicochemical parameters of anti-insulin antibodies in her serum are discussed.
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PMID:A case of diabetes mellitus associated with anti-insulin autoantibodies without previous insulin injection. 331 66

In order to better understand the role of A- and B-cell function in diabetic pregnancy, we studied four groups of pregnant women at week 34-36 of gestation. Seventeen were healthy controls (C), 24 had gestational diabetes (GD), 16 had type 2 diabetes (NIDD) and 37 had type 1 diabetes (IDD). At times -20, 0, 20, 30, 45, 60, 90 and 120 min from the beginning of a 30 min infusion of 30 g of arginine intravenously, plasma glucose, glucagon (IRG) and C-peptide (CPR) were measured. Plasma glucose was higher in diabetic than in control subjects. IRG values were also higher in the GD and the NIDD women. CPR values were similar to, or slightly higher than control values in the GD and the NIDD and were much lower in the IDD women. All three variables increased during the arginine infusion in all groups, with the exception that CPR remained unchanged in the IDD. The CPR/IRG molar ratio was similar in control, GD and NIDD women; in the IDD, it was much smaller than in the other groups and was not affected by arginine. In all the diabetic patients, IRG was negatively correlated with the maternal weight gain and in the IDD IRG was positively correlated with the increase in the insulin need and with the CPR levels. In conclusion diabetes appeared to enhance the A-cell function also in pregnancy, possibly impairing the 'facilitated anabolism' and stressing the 'accelerated starvation' which are typical of normal pregnancy. Glucagon was confirmed as one possible determinant of the insulin resistance seen in diabetic pregnancy.
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PMID:Endocrine pancreatic function in insulin-dependent diabetic pregnant women. 353 67

A 31-year-old woman with Graves' disease developed fasting hypoglycemia after treatment for 3 weeks with methimazole. Although the patient had not received exogenous insulin, high titers of insulin autoantibodies were found in serum and large amounts of total and free insulin (1550 and 82 microU/ml, respectively) and C-peptide reactivity (CPR, 22 ng/ml) were detected in serum. After glucose loading, blood glucose and total insulin levels increased abnormally. The immunoglobulin class of the autoantibodies was IgG and the light chains were of the kappa type. The titers of insulin autoantibodies, elevated serum total and free insulin, and CPR levels decreased gradually, but insulin autoantibodies and elevated insulin levels were still present in the serum 8 months after the episode of hypoglycemia. These findings suggest that the patient's fasting hypoglycemia was due to excess free insulin released from antibody-bound insulin, and that methimazole might play a role in the initiation of production of insulin autoantibodies.
Diabetes Res Clin Pract
PMID:Spontaneous hypoglycemia and insulin autoantibodies in a patient with Graves' disease. 359 31

In vivo insulin clearance in 10 subjects with non-insulin-dependent diabetes mellitus (NIDDM) has been compared with clearance in eight equally obese nondiabetic control subjects by two different methods. The first approach consisted of determining the metabolic clearance rates of exogenously infused insulin (MCRI) during hyperinsulinemic (100 mU/m2/min) glucose clamp studies. The results indicated that mean (+/- SEM) MCRI was 1.4-fold greater in the diabetic subjects (436 +/- 22 ml/m2/min) than in the controls (325 +/- 24 ml/m2/min, P less than 0.005), resulting in a lower steady-state plasma insulin concentration in the diabetic (255 +/- 8 microU/ml) compared with the nondiabetic subjects (329 +/- 29 microU/ml, P less than 0.001). The impact of NIDDM on insulin removal rates was also estimated by a second method in which extraction of endogenously secreted insulin (EXTI) in response to an oral glucose load was calculated from the integrated area above basal of plasma insulin (IRI) and of plasma C-peptide (CPR), an estimate of beta-cell secretion. The results demonstrated that fractional extraction of endogenously secreted insulin (EXTI = 100 [(CPR - IRI)/CPR]) was also 1.2-fold greater for diabetic subjects (88.9 +/- 2.5%) than for nondiabetic controls (72.0 +/- 2.8%, P less than 0.001). Finally, these two independent measurements of in vivo insulin removal rates (MCRI and EXTI) were significantly correlated with each other (r = 0.71, P less than 0.002). These observations are consistent with the view that elevated insulin clearance may contribute to the postchallenge hypoinsulinemia of NIDDM in Pima Indians.
Diabetes 1985 Jul
PMID:Elevated in vivo insulin clearance in pima indians with non-insulin-dependent diabetes mellitus. 389 74

The prevalence of islet cell surface antibodies (ICSA) in patients with insulin-dependent (IDD), noninsulin-dependent (NIDD) or newly-diagnosed diabetes mellitus was studied. The antibodies were present in 14 (27%) of 15 IDD patients below the age of 30 years, and in 11 (12%) of 91 NIDD patients. Among 46 newly-diagnosed diabetic patients, (aged over 30 years), 14 (30%) were antibody-positive and had a fasting blood sugar exceeding 11 mmol glucose. The glucose tolerance after a standardized breakfast decreased in IDD or insulin-treated patients with ICSA compared to patients without antibodies. C-peptide was also lower in patients with circulating ICSA (xi CPR/xi BS during a standardized breakfast test 0.61 +/- 0.30 vs. 1.09 +/- 0.3 in IDD, 1.18 +/- 0.13 vs. 1.46 +/- 0.43 in the patients with insulin treatment). These results suggest that circulating ICSA be also present in some newly-diagnosed patients of over 30 years of age who require insulin treatment and who have an associated decreased glucose tolerance and C-peptide response.
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PMID:Islet cell surface antibodies in diabetes and their possible influence on glucose tolerance. 637 61

Serum free C-peptide immunoreactivities (serum free CPR) during a 100 g oral glucose tolerance test (OGTT) were measured in 21 patients with insulin-dependent diabetes mellitus (IDDM, with abrupt onset and ketosis-prone), 57 insulin-treated patients with noninsulin-dependent diabetes mellitus ( INIDDM , with gradual onset and not ketosis-prone), 39 oral hypoglycemic agent-treated patients with noninsulin-dependent diabetes mellitus ( ONIDDM ) and 9 healthy young men for control study. Although the fasting blood glucose value of the INIDDM group was not significantly different from that of the IDDM and ONIDDM groups, the free CPR response at each interval during OGTT in the INIDDM group was significantly higher than that in the IDDM group and lower than that in the ONIDDM group. The sum of serum free CPR during OGTT (sigma serum free CPR) was found to be negatively correlated to the duration of insulin treatment either in bivariate or multivariate analysis in INIDDM patients. Using 9.5 ng/ml as an index, all sigma serum free CPR values in the ONIDDM group were above this index, whereas all the values except one in the IDDM group were below it. The values in the INIDDM were scattered within the ranges of the other two groups. The insulinogenic index delta serum free CPR/delta blood glucose (30 min-fasting) of the ONIDDM group was significantly lower than that of normal subjects, although sigma serum free CPR values were not significantly different. The results indicate that: 1. Residual pancreatic B-cell function in INIDDM patients is lower than that in ONIDDM patients and is negatively correlated to the duration of insulin treatment in INIDDM patients. 2. Measuring serum free CPR may be a discriminative method for establishing insulin dependency in insulin-treated patients. 3. Impairment of early insulin secretion after the oral glucose load is a distinguished characteristic of diabetic patients.
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PMID:A study of serum free C-peptide responses to oral glucose load in diabetic patients: with special reference to types of diabetes and methods of treatment. 637 68


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