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)

The expression and regulation of IGF-I is tissue-specific in diabetes mellitus in the rat. These studies were designed to examine if similar tissue specificity exists for IGF-BPs in the diabetic milieu. Diabetes mellitus was induced by a single i.p. injection of STZ (100 mg/kg body weight). Rats were treated with either vehicle--insulin, vanadate, or phlorizin for 7-14 days. Tissues were analyzed for IGF-BPs by ligand blotting and by affinity cross-linking and immunoprecipitation. In liver tissue from nondiabetic control rats, multiple forms of IGF-BPs were noted, ranging from 48,000 to 25,000 M(r). In diabetic rat liver tissue, the 25,000-M(r) form was unchanged, whereas the higher M(r) forms (48,000-42,000 M(r)) were decreased, and the 30,000-M(r) form was increased. Insulin therapy of diabetic rats decreased all forms to below control levels. In the kidney tissue of control rats, faint IGF-BP bands were seen at 30,000 and 25,000 M(r). In diabetic rat kidney tissue, the 30,000-M(r) form again was increased (as in liver) and restored to control levels with insulin therapy. In contrast, only a 30,000-M(r) band was seen in control pituitary tissue, which was slightly increased in the diabetic rats and also was decreased below control levels by insulin. In hypothalamus and cerebral cortex tissue, bands at 30,000 and 25,000 M(r) were noted, and neither was altered by diabetes or insulin treatment. Treatment of diabetic rats with vanadate and phlorizin resulted in comparable blood glucose levels, which were only slightly higher than those achieved with insulin therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1992 Dec
PMID:Differential tissue regulation of insulin-like growth factor binding proteins in experimental diabetes mellitus in the rat. 128 Feb 36

The steady-state levels of mRNA encoding for the alpha 1(IV) collagen chain, laminin B1 and B2 chains, basement membrane HSPG, and alpha 1(I) and alpha 1(III) collagen chains were examined in rat glomeruli at 4, 12, and 24 wk after injection of STZ. The mRNA levels for the alpha 1(IV) collagen chain, laminin B1 and B2 chains, and alpha 1(I) and alpha 1(III) collagen chains increased significantly with age in the STZ-induced diabetic rats before morphological thickening of basement membrane occurred. In contrast, the mRNA levels for HSPG decreased markedly 4 wk after STZ injection and then increased with age compared with those for control rats. The mRNA levels for these ECM components showed a continuous decline with age in controls. Treating the diabetic rats with insulin for 4 wk ameliorated the abnormally regulated ECM gene expression in the glomeruli. These data suggest that the abnormal regulation of ECM gene expression in the glomeruli may contribute to the expansion of mesangial matrix and basement membrane thickening in diabetic rats, and that hyperglycemia may play a role in the abnormal ECM gene expression.
Diabetes 1992 Dec
PMID:ECM gene expression and its modulation by insulin in diabetic rats. 128 Feb 37

Insulinopenic states in rodents are known to cause an increase in the number of hepatic insulin receptors. To determine if this change is related to an abnormality in insulin receptor gene expression, insulin receptor binding, insulin receptor mRNA levels, and insulin receptor gene transcription rates have been measured in livers from rats rendered hypoinsulinemic by STZ administration (65 mg/kg) or fasting. In the two groups of experimental rats, insulin binding to liver plasma membranes was increased (approximately 40 and 25%, respectively) relative to control, normoinsulinemic animals. Northern blot analysis of either total or poly (A)+ RNA from livers of hypo- and normoinsulinemic rats revealed two major insulin receptor mRNA species of 9.5 and 7.5 kbs. In hypoinsulinemic rats, insulin receptor mRNA levels were increased > or = 10-fold, with similar effects on the two mRNA species. The effects of STZ administration and fasting on insulin receptor binding and insulin receptor mRNA levels were fully reversed by insulin treatment or refeeding, respectively. Injection of ACT D, an inhibitor of gene transcription, decreased insulin receptor mRNA levels by > or = 80% in control and diabetic rats and suppressed the overexpression of mRNA seen in diabetic rats. In vitro nuclear transcription assays showed that the rate of transcription of the insulin receptor gene was increased 2-fold in STZ-induced diabetic rats and fasted rats relative to control animals. Taken together, these results suggest that the upregulation of the insulin receptor induced by chronic insulinopenia results, at least in part, from an increase in insulin receptor gene transcription.
Diabetes 1992 Dec
PMID:Effects of STZ-induced diabetes and fasting on insulin receptor mRNA expression and insulin receptor gene transcription in rat liver. 128 Feb 38

The mechanism regulating lipoprotein lipase (LPL) expression in adipose tissue was examined in rats in the conditions of different calorie intakes with and without streptozotocin-induced (STZ-) diabetes. The LPL activity released from adipose tissue was greater with the higher calorie intake (20 g of normal chow diet per day) than with the lower calorie intake (13 g of normal chow diet per day), and was greater in normal rats than in STZ-diabetic rats. The LPL activity was proportional to the serum insulin level in all conditions. Dot-blot analysis showed that the amount of LPL mRNA in adipose tissue was increased by the higher calorie diet and that the increase was less in the diabetic state. Expression of mRNA was also nearly parallel with the serum insulin level. LPL activity released from the heart was not affected by either the calorie intake or the diabetic state. These results suggest that the mechanisms of LPL expression in adipose tissue and the heart are different, and that LPL expression in adipose tissue was closely dependent on the insulin level.
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PMID:Response of lipoprotein lipase to calorie intake in streptozotocin-induced diabetic rats. 128 30

The use of microelectrode techniques for studying oxygen distribution and blood flow in the eye of a physiologically well maintained rat provides a very convenient model in which to study oxygen supply to the retina. The availability of rat models of vascular disease such as diabetes and hypertension, and the existence of several models of retinal degeneration, make studies of oxygen supply in the rat eye of particular relevance. The experiments reported in this paper demonstrate changes in oxygen distribution and blood flow very early in STZ induced diabetes. Thus, we have established a preparation in which the role of changes in oxygen supply can be correlated with the pathological events that are apparent later in the disease.
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PMID:Oxygen tension and blood flow in the retina of normal and diabetic rats. 128 5

To investigate the possible mechanisms of the alterations in morphine-induced analgesia observed in diabetic mice, we examined the influence of streptozotocin-induced (STZ-induced) diabetes on analgesia mediated by the different opioid receptors. The antinociceptive potency of morphine (10 mg/kg), administered s.c., as determined by both the tail-pinch and the tail-flick test, was significantly reduced in diabetic mice as compared to that in controls. Mice with STZ-induced diabetes had significantly decreased sensitivity to intracerebroventricularly (i.c.v.) administered mu-opioid agonists, such as morphine (10 micrograms) and [D-Ala2,N-Me Phe4,Gly-ol5]enkephalin (DAMGO, 0.5 micrograms). However, i.c.v. administration of [D-Pen2,5]enkephalin (DPDPE, 5 micrograms), a delta-opioid agonist, and U-50,488H (50 micrograms), a kappa-opioid agonist, produced pronounced antinociception in both control and diabetic mice. Furthermore, there were no significant differences in antinociceptive potency between diabetic and control mice when morphine (1 microgram), DAMGO (10 micrograms), DPDPE (0.5 micrograms) or U-50,488H (50 micrograms) was administered intrathecally. In conclusion, mice with STZ-induced diabetes are selectively hyporesponsive to supraspinal mu-opioid receptor-mediated antinociception, but they are normally responsive to activation of delta- and kappa-opioid receptors.
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PMID:Streptozotocin-induced diabetes selectively alters the potency of analgesia produced by mu-opioid agonists, but not by delta- and kappa-opioid agonists. 131 65

The effects of physical training on beta-adrenergic-receptor density (Bmax) and adenylate cyclase (AC) activity in soleus muscles (type I) and the deep red portion (type IIa) and superficial white portion (type IIb) of vastus lateralis muscles in diabetic rats were investigated. Rats were rendered diabetic with streptozotocin ([STZ] 45 mg/kg intravenously [IV]) and were either kept sedentary ([SD] n = 12) or submitted to a progressive 10-week treadmill running program ([TD] n = 13). A group of normal sedentary rats served as controls ([SC] n = 13). Plasma glucose levels were increased in SD rats in comparison with SC rats (21.3 +/- 1.4 mmol/L v 7.7 +/- 0.2; mean +/- SE, P < .001), but levels were partially reversed to normal by training (10.7 +/- 1.7; P < .01 v SD). The gastrocnemius nicotinamide adenine dinucleotide (NAD)-isocitrate dehydrogenase (ICDH) activity was significantly increased in TD rats in comparison to SC or SD rats (P < .001). The Bmax and antagonist affinity (Kd) determined with 125iodocyanopindolol (ICYP) were not affected by diabetes in any of the three types of muscle. In type I muscle, TD rats showed a significant 67% increase in Bmax compared with that of SD rats (TD 26.7 +/- 2.0 v SD 16.0 +/- 1.0; P < .001). In type IIa muscle, Bmax was significantly higher by 68% in TD rats as compared with SD rats (TD 16.5 +/- 1.7 v SD 9.8 +/- 0.9 fmol/mg protein; P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Physical training increases beta-adrenoceptor density and adenylate cyclase activity in high-oxidative skeletal muscle of diabetic rats. 133 10

Histomorphometric examination and histological observation of femoral bone were performed on long-standing neonatal streptozotocin-induced diabetic rats (n2STZ, n5STZ) as a human model of non-insulin-dependent diabetes mellitus. The growth and strength of femurs decreased in the STZ diabetic rats. Histomorphometric parameters such as cortical bone thickness, number of metaphysical trabeculae and percent trabecular volume of metaphysical area all significantly decreased in the STZ diabetic rats. There were no significant differences in parameters between the n2STZ and n5STZ diabetic rats. Histological findings demonstrated no significant change in the number of osteoclasts in femur nor change corresponding to osteomalacia. Bone absorption in the STZ diabetic rats appeared unchanged. The plasma calcium level did not change in the STZ diabetic rats, although their plasma phosphate or A1-p levels increased. Circulating 24, 25 (OH)2D3 was significantly lower in the STZ diabetic rats than the controls. However, 25 (OH) D3 or biologically active 1, 25 (OH)2D3 was not different between the controls and STZ diabetic rats. Osteopenia is thus present in the femurs of long-standing neonatal STZ diabetic rats, due in part to abnormal vitamin D metabolism.
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PMID:Alterations in femoral bone histomorphometry and vitamin D metabolism in neonatal streptozotocin-induced diabetic rat. 133 71

Spontaneously hypertensive rats (SHR) were injected with streptozotocin (STZ-SHR) to induce diabetes. The effect of DP-1904, a thromboxane A2 synthetase inhibitor, on diabetic nephropathy was then studied by administering it for 5 months (1 or 10 mg/kg). DP-1904 did not affect renal 6-keto prostaglandin (PG)F1 alpha production in STZ-SHR, but markedly inhibited renal thromboxane (TX) B2 production, so that the 6-keto PGF1 alpha/TXB2 ratio was significantly increased (P less than 0.05). STZ-SHR showed significant uraemia and proteinuria, plus increases in urinary gamma-glutamyl-transpeptidase and urinary N-acetyl-beta-glucosaminidase. DP-1904 significantly decreased (P less than 0.01) the urinary changes. STZ-SHR also showed an increase in mesangial periodic acid-Schiff-positive substance and in relative renal weight, both of which were significantly inhibited by DP-1904 (P less than 0.05). Thus, DP-1904 inhibited both TXB2 production and the progression of renal damage in STZ-SHR.
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PMID:A thromboxane A2 synthetase inhibitor retards hypertensive rat diabetic nephropathy. 135 Sep 91

Experimental diabetes mellitus was induced in adult male rats by injecting streptozotocin (STZ; 60 mg/kg iv) for the purpose of surveying changes in the pharmacokinetics of biliary excretion after the intravenous administration of 40 mg/kg of cefoperazone (CPZ) or cephradine (CED). CPZ, CED, and other organic anions share affinity for the organic anion transport system in the bile canalicular membrane. The STZ treatment had a marked influence on the distribution and elimination of both cephalosporins. The blood levels of both cephalosporins at each time point after administration differed significantly between the STZ-treated and control rats. The values of mean residence time (MRT) of CPZ and CED were significantly decreased in the STZ-treated rats. Basal bile flow rates were increased after the administration of CPZ in the control and STZ-treated rats. Biliary clearance (CLbile) of CPZ was more than 60% of the CLtot, whereas CLbile of CED was less than 20% of CLtot in both groups of rats. The mean CLbile value of CPZ in the STZ-treated rats was 1.0 ml/min higher than that of the control rats, whereas the mean CLbile value of CED was almost the same as that of the control rats. The increased CLbile of CPZ suggested that diabetes alters the biliary excretion of CPZ. The changes in MRT of CPZ in the STZ-treated and control rats are mainly caused by an increase in the biliary excretory rate and renal clearance. The changes in MRT of CED in the STZ-treated and control rats are caused by a decrease in the apparent volume of distribution and increased renal clearance.
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PMID:Comparative pharmacokinetics of cefoperazone and cephradine in untreated streptozotocin diabetic rats. 135 79


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