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)

Thirty-six hypertensive patients with impaired renal function entered a long-term study to assess the safety of perindopril. There were 28 men and 8 women of mean age 57.1 +/- 2.0 years (mean +/- SEM). The duration of documented hypertension was 7.3 +/- 1.2 years. Perindopril was given orally in single daily doses. The initial dosage was chosen according to the degree of renal function impairment: 29 patients received 4 mg o.d. [creatinine clearance (Clcr), 42.2 +/- 3.2 ml.min-1] and 7 patients received 2 mg o.d. (Clcr, 22.3 +/- 3.1 ml.min-1). Patients in whom blood pressure was not controlled had their dose doubled and then, if necessary, an additional diuretic therapy was added at subsequent visits. Six patients were withdrawn for adverse events (myocardial infarction, pneumonia, leucopenia in a patient who had lupus, diabetes mellitus, skin rash, epigastric pain), two patients were withdrawn for poor compliance, and three for personal convenience. The mean duration of treatment was 10.2 months with a range of 3-12 months (excluding one patient who died from myocardial infarction in the first days of the study and was not included in the analysis). Systolic and diastolic blood pressure decreased significantly (from 170.5/100.6 +/- 3.4/1.8 mm Hg to 151.8/88.8 +/- 3.0/1.7 mm Hg, n = 35, p less than 0.001). Baseline and final values of plasma creatinine (from 223.7 +/- 22.7 to 234.7 +/- 28.5 mumols/l), Clcr (42.5 +/- 3.2 to 45.7 +/- 4.6 ml.min-1), and kalemia (from 4.4 +/- 0.1 to 4.7 +/- 0.1 mmol/L) were not statistically different.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Long-term tolerance of perindopril in hypertensive patients with impaired renal function. 172 1

Using a highly sensitive radioimmunoassay, elevated plasma immunoreactive endothelin (ir-ET) levels were found in patients with diabetes mellitus (1.88 +/- 0.12 pmol/L, mean +/- SEM, n = 100), patients undergoing maintenance hemodialysis (4.28 +/- 0.76 pmol/L, n = 14), patients with acute myocardial infarction (3.43 +/- 1.03 pmol/L, n = 6), and patients with subarachnoid hemorrhage (4.92 +/- 0.64 pmol/L, n = 14) (normal controls: 0.54 +/- 0.05 pmol/L, n = 19). ir-ET was also present in urine (2.1 +/- 0.3 pmol/L, n = 12), breast milk (6.8 +/- 1.6 pmol/L, n = 16), and saliva (2.0 +/- 0.2 pmol/L, n = 15) obtained from healthy subjects. Chromatography studies verify the identity of endothelin. Fast protein liquid chromatography (FPLC) showed one peak in the normal plasma extract, three peaks in the plasma extracts from diabetic patients and patients undergoing maintenance hemodialysis, three peaks in the urine extract, four peaks in the milk extract, and five peaks in the saliva extract. When the materials eluting in the void volume on FPLC of urine and saliva extracts were loaded onto a Sephadex G-25 column, the ir-ET was eluted in a higher molecular weight region. Incubation of endothelin-1, endothelin-2, and endothelin-3 in urine for 5 h showed that the total amount of ir-ET decreased to less than 30% of the initial levels, suggesting that endothelins are very unstable in urine.
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PMID:Immunoreactive endothelin in human plasma, urine, milk, and saliva. 172 88

Immunoreactive (ir)-endothelin (ET) in urine was studied with a radioimmunoassay in patients with diabetes mellitus (DM) and non-DM diseases including endocrine disorders, primary glomerular diseases, autoimmune diseases, and hematological malignancies. Twenty-four-hour excretions (mean +/- SEM) of ir-ET were 8.0 +/- 0.9 pmol/day in the DM group (n = 13) and 9.5 +/- 1.2 pmol/day in the non-DM group (n = 51). No significant differences among DM and other disease groups were noted with respect to 24-h ir-ET excretion. Reverse-phase high-performance liquid chromatography of a normal urine extract revealed a major peak eluting later than ET-1. Gel chromatography revealed a single major peak in a smaller molecular weight (MW) region in normal urine and an additional peak in larger MW region in a urine extract from a DM patient. Urinary ir-ET consists of at least two components which may be metabolites of ET or ET precursors in plasma or peptides derived from the kidney.
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PMID:Immunoreactive endothelin in urine of patients with and without diabetes mellitus. 172 99

Permselective acrylic membranes were employed to prevent immune rejection of discordant islet xenografts isolated from various large animals. Canine, porcine, and bovine islets were seeded into tubular diffusion chambers and transplanted into the peritoneum of 27 nonimmunosuppressed streptozotocin-induced diabetic Lewis rats. Six recipients received islet grafts from bovine calves, 7 received grafts from pigs, and 14 received grafts from dogs. Four of the latter were removed at 1 month. In the control group of 10 diabetic rats, 4 received nonencapsulated canine islets, 3 received nonencapsulated bovine islets, and 3 received nonencapsulated porcine islets. Recipients of encapsulated islets promptly dropped from a pretransplantation plasma glucose level of 487 +/- 36 (mean +/- SEM) to 84 +/- 2 (canine), 81 +/- 4 (bovine), and 81 +/- 3 mg/dl (porcine) during the first week. All of the animals sustained these levels for at least 1 month. One rat spontaneously reverted to diabetes at 54 days posttransplantation; 4 other rats became hyperglycemic (glucose, greater than 600 mg/dl) after membrane removal on day 30. The remaining 22 rats maintained fasting euglycemia for greater than 10 weeks. In contrast, rats that received nonencapsulated islets became hyperglycemic in less than 7 days. Intravenous glucose tolerance test K values (decline in glucose levels, %/min) at 1 month for the canine and bovine encapsulated islet transplant group were 3.5 +/- 0.3 and 3.3 +/- 0.1 compared with 3.3 +/- 0.1 (P = 0.63) and 0.91 +/- 0.1 (P less than 0.0001) for normal (n = 4) and diabetic (n = 4) control groups. Morphologic studies of long-term functioning grafts (30-130 days) revealed well-preserved alpha, beta, and delta cells, with varying degrees of granulation. These results demonstrate that immune isolation of islet tissue using permselective artificial membranes can protect discordant islet xenografts from immune rejection in the absence of any immunosuppressive drugs.
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PMID:Xenotransplantation of canine, bovine, and porcine islets in diabetic rats without immunosuppression. 176 25

The biological effects of a hormone are dependent on the concentration delivered to the target tissue. This is generally best reflected in the arterial concentration. However, the liver is unique in that it receives substantial additional blood flow from the portal venous system. This may be important in the case of the catecholamines, where extraction or spillover from the splanchnic circulation may occur. In this study we examined portal venous catecholamine concentrations in anesthetized, laparotomized rabbits. We compared the values with simultaneously sampled arterial levels to evaluate the effects of the splanchnic tissues upon a wide range of catecholamine concentrations delivered to the liver during a state of stress. Spillover of norepinephrine and extraction of epinephrine were observed in all rabbits. Mean (+/- SEM) arterial norepinephrine concentrations were elevated, 716 +/- 167 pg/ml (n = 11); mean portal concentrations were 178 +/- 37% higher (p less than 0.01), at 1,425 +/- 301 pg/ml, representing net spillover from splanchnic tissues. In addition, significant extraction of epinephrine was observed; arterial concentrations were 2,144 +/- 580 pg/ml (n = 11). Portal levels were 1,205 +/- 382 pg/ml, 38 +/- 7.45% lower than corresponding arterial concentrations (p less than 0.02). Furthermore, there was a concentration-dependent effect upon norepinephrine spillover; the highest arterial norepinephrine concentrations were associated with the lowest splanchnic spillover. This resulted in a negative correlation between the arterial norepinephrine levels and the percent increase from spillover into the portal vein (r = -0.81, p less than 0.003). We conclude that portal venous catecholamine concentrations are significantly different from arterial levels in anesthetized, laparotomized rabbits over a wide range of concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes Res 1991 Apr
PMID:Catecholamine concentrations in the hepatic portal system: effect of surgical stress upon portal levels. 180 84

Lipid and apoprotein composition of four very low density lipoprotein (VLDL) subfractions decreasing in Sf value were evaluated in the fasting state in 12 normolipidemic Pima Indians (6 M, 6 F, age 39 +/- 1.7 yrs) (mean +/- SEM) with non-insulin-dependent diabetes mellitus (NIDDM) in poor glycemic control (HbA1 9.8 +/- 2.9%) and in 14 normoglycemic Pima controls matched for age, BMI and lipid values. Total cholesterol (CHOL), triglyceride (TG), phospholipids (PL), total protein (TP), apo B, apo CII, apo CIII and apoE were assayed in total VLDL and in each of the four VLDL subfractions designed as A (Sf greater than 400), B (Sf 175-400), C (Sf 100-175), and D (Sf 20-100). Diabetics compared to nondiabetics had higher concentrations of all constituents of VLDL D, with the largest changes being in TG (38.0 +/- 3.8 vs 28.0 +/- 2.5 mg/dl, P less than 0.04), PL (14.0 +/- 1.3 vs 10.0 +/- 1.0 mg/dl, P less than 0.04), TP (9.8 +/- 0.8 vs 7.6 +/- 2.4 mg/dl, P less than 0.05), apo B (6.3 +/- 0.5 vs 4.7 +/- 0.4 mg/dl, P less than 0.03) and apoE (0.73 +/- 0.09 vs 0.52 +/- 0.04 mg/dl, P less than 0.04). Since no difference was found between the groups in percentage composition of lipids or apoproteins in total VLDL and in all VLDL subfractions, the data suggest that in diabetics, even when normolipidemic, there is an increase in the number rather than in the composition of the smallest VLDL subfraction (VLDL D), which are usually considered to be more atherogenic.
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PMID:Alterations in very low density lipoprotein subfractions in normotriglyceridemic non-insulin-dependent diabetics. 181 50

We studied the long-term change in glycemic level in a model of non-insulin-dependent diabetes mellitus (NIDDM) induced by neonatal streptozotocin (STZ) treatment in spontaneously hypertensive rats (SHR). Two-day-old male SHR were intraperitoneally injected with 37.5 to 75.0 mg/kg of STZ or vehicle alone as control. According to nonfasting plasma glucose levels at 12 weeks of age, rats were divided into mild (less than 16.8 mmol/L) and severe (greater than or equal to 16.8 mmol/L) diabetes groups. In the mild diabetes group (n = 5), plasma glucose decreased significantly from 14.2 +/- 1.8 mmol/L (mean +/- SEM) at 20 weeks to 7.3 +/- 0.3 mmol/L at 52 weeks (P less than .05) with progressing age. At 52 weeks, overnight fasting plasma glucose levels were significantly lower and serum immunoreactive insulin (IRI) was higher than in controls, respectively (4.1 +/- 0.3 v 5.7 +/- 0.3 mmol/L, P less than 0.01; 625 +/- 50 v 409 +/- 50 pmol/L, P less than .05), and insulinoma was found in 60% of rats. Therefore, the recovery from hyperglycemia may be attributed to the development of insulinoma. In the severe diabetes group (n = 6), plasma glucose remained high until 28 weeks (27.2 +/- 1.5 mmol/L), but thereafter decreased with age, as it did in the mild diabetes group (13.7 +/- 3.5 mmol/L at 52 weeks, P less than .005). However, no insulinoma was found, and the mechanism for the recovery was unclear. The present study demonstrates that hyperglycemia spontaneously ameliorates in a neonatal STZ diabetes model of SHR, although this phenomenon may be strain-related.
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PMID:Spontaneous recovery from non-insulin-dependent diabetes mellitus induced by neonatal streptozotocin treatment in spontaneously hypertensive rats. 182 2

Streptozotocin (STZ) treatment on neonatal rats produces a non-insulin-dependent diabetes mellitus (NIDDM) model in adulthood. Applying this model to spontaneously hypertensive rats (SHR), we designed the present study to develop a new model of NIDDM with genetic hypertension. Two-day-old male and female SHR were intraperitoneally injected with 25.0-75.0mg/kg STZ, and two-day-old Wistar Kyoto rats (WKY) of both sexes, which are a normotensive control strain for SHR, were similarly injected with 75.0-150.0mg/kg STZ. Control rats received vehicle alone. The relationships between the doses of the STZ injected and the changes of the metabolic variable and blood pressure were examined for 12 weeks following the treatment. Plasma glucose levels in male SHR increased in a dose-dependent manner at 12 weeks, control 122 +/- 8 (SEM) mg/dl, 25.0mg/kg STZ 139 +/- 13mg/dl (ns), 37.5mg/kg STZ 240 +/- 51mg/dl (ns), 50.0mg/kg STZ 359 +/- 39mg/dl (p less than 0.01), 62.5mg/kg STZ 419 +/- 33mg/dl (p less than 0.001) and 75.0mg/kg STZ 513 +/- 10mg/dl (p less than 0.001), whereas in male WKY, only mild hyperglycemia developed in case of the higher doses of STZ given, control 112 +/- 4mg/dl, 75.0mg/kg STZ 136 +/- 18mg/dl (ns), 100.0mg/kg STZ 204 +/- 40mg/dl (ns), 125.0mg/kg STZ 219 +/- 37mg/dl (p less than 0.05), and 150.0mg/kg STZ 177 +/- 12mg/dl (p less than 0.01). The development of hypertension was not affected by the neonatal STZ treatment in male SHR at 11 weeks, systolic blood pressure being control 210 +/- 7mmHg, 25.0mg/kg STZ 217 +/- 5mmHg (ns), 37.5mg/kg STZ 202 +/- 3mmHg (ns), 50.0mg/kg STZ 216 +/- 6mmHg (ns), 62.5mg/kg STZ 210 +/- 6mmHg (ns), and 75.0mg/kg STZ 209 +/- 5mmHg (ns). For the long-term observation, STZ-treated male SHR were divided into mild diabetes group (plasma glucose at 12 weeks less than 300mg/dl, mean 195 +/- 21mg/dl) and severe diabetes group (greater than or equal to 300mg/dl, mean 445 +/- 18mg/dl). Hyperglycemia in both groups was maintained until 28 weeks, plasma glucose being control 112 +/- 4mg/dl, mild diabetes group 161 +/- 10mg/dl (p less than 0.01), and severe diabetes group 419 +/- 25mg/dl (p less than 0.001) but it later gradually ameliorated, plasma glucose at 52 weeks being control 120 +/- 3mg/dl, mild diabetes group 131 +/- 7mg/dl (ns), and severe diabetes group 220 +/- 43mg/dl (ns). However, hypertension persisted in both diabetes groups until 52 weeks, systolic blood pressure being control 209 +/- 6mmHg, mild diabetes group 199 +/- 9mmHg (ns), and severe diabetes group 221 +/- 6mmHg (ns).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:A new animal model of non-insulin-dependent diabetes mellitus with hypertension: neonatal streptozotocin treatment in spontaneously hypertensive rats. 183 97

We have previously reported on plant mixture extract comprising of Nigella sativa, Myrrh, Gum Olibanum, Gum Asafoetida and Aloe to have a blood glucose lowering effect. The present study with streptozotocin diabetic rats is focussed on the mechanism of action, specifically on a) hepatic gluconeogenesis b) activity of key gluconeogenic enzymes, pyruvate carboxylase (PC) and phosphoenol-pyruvate carboxykinase (PEPCK). Similar studies using a biguanide, phenformin, have been conducted to compare the mode of action of these two compounds. The blood glucose levels (mean +/- SEM) before and after treatment with the plants extract were (16.7 +/- 1.7 mmol/L and 8.5 +/- 1.3 mmol/L) and with phenformin (15.1 +/- 1.3 mmol/L and 10.7 +/- 1.5 mmol/L). The rate of gluconeogenesis in isolated hepatocytes as well as activity of PC and PEPCK in liver homogenates is significantly lowered following treatment with the plants extract. Although phenformin also lowers blood glucose, it does not affect hepatic gluconeogenesis under stated experimental conditions. It is concluded that the anti-diabetic action of the plants extract may, at least partly, be mediated through decreased hepatic gluconeogenesis. The extract may prove to be a useful therapeutic agent in the treatment of non-insulin dependent diabetes mellitus (NIDDM).
Diabetes Res 1991 Dec
PMID:The effect of a plants mixture extract on liver gluconeogenesis in streptozotocin induced diabetic rats. 184 51

1. The effects of acute hypoglycaemia on haemostasis, fibrinolysis, blood viscosity and erythrocyte aggregation were examined after acute insulin-induced hypoglycaemia in six normal male subjects and in six male patients with poorly controlled insulin-dependent diabetes. In the control subjects hypoglycaemia caused a significant increase in the concentration of von Willebrand factor, with no change in the concentrations of fibrinogen and cross-linked fibrin degradation products. Fibrinolysis was enhanced, as indicated by significant increases in tissue plasminogen activator concentration and the fibrin plate lysis area, with a fall in plasminogen-activator inhibitor activity, suggesting complex formation. Whole-blood and plasma viscosity increased significantly after hypoglycaemia, but there was no significant change in erythrocyte aggregation tendency. 2. In diabetic patients the increase in the concentration of von Willebrand factor was significantly greater than in the control group (analysis of variance, P less than 0.02). The basal concentration of tissue plasminogen activator was reduced at 3.7 +/- 0.7 mg/l (mean +/- SEM) in the diabetic group compared with 8.5 +/- 1.3 mg/l in the control group (Student's t-test, P less than 0.01), but thereafter the increase in response to hypoglycaemia was similar. The changes in the other variables were not significantly different from the changes in the control group. 3. During acute hypoglycaemia in poorly controlled diabetic patients there is promotion of haemostasis with a greater increase in the concentration of von Willebrand factor, which, in association with the increase in viscosity, might reduce perfusion in diabetic microangiopathy, leading to aggravation of the microvascular complications of diabetes.
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PMID:Effects of acute insulin-induced hypoglycaemia on haemostasis, fibrinolysis and haemorheology in insulin-dependent diabetic patients and control subjects. 185 95


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