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

Plasma lipids and cardiac performance were studied in diabetic rats treated with probucol. Male Wistar rats were rendered diabetic with a single intraperitoneal injection of streptozotocin (STZ, 75 mg/kg). Nondiabetic control rats received the vehicle alone. Two weeks after STZ or vehicle injection, control and diabetic rats were randomly assigned to probucol-treated or untreated groups. The rats in the two probucol-treated groups (control- and diabetic-probucol groups) were fed a diet containing 1% probucol (w/w) for 4 weeks. Blood was drawn, and then cardiac performance was assessed by the isolated perfused working heart technique. Probucol treatment had no effect on the cardiac performance of the nondiabetic control rats. The peak left ventricular developed pressure and maximum rate of change in left ventricular pressure during systole were significantly greater in the probucol-treated diabetic rats than in the untreated diabetic rats (p less than 0.05), although cardiac performance did not improve to the level in the nondiabetic rats. Plasma cholesterol, free fatty acid, and phospholipid were significantly elevated in the untreated diabetic rats, and probucol treatment decreased significantly the plasma cholesterol and free fatty acid concentrations (p less than 0.05). These data suggest that probucol treatment improves plasma lipids and cardiac performance in rats with experimental diabetes and may prevent diabetic cardiomyopathy.
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PMID:Effects of probucol on impaired cardiac performance and lipid metabolism in streptozotocin-induced diabetic rats. 138 Oct 8

Adrenal growth occurs in experimental diabetes, and evidence exists for increased adrenal function. The concentration of PPRibP has been examined in the rat adrenal gland at various times after induction of diabetes with STZ, in view of the key role it plays in the synthesis of Purs and Pyrs. The PPRibP level was exceptionally high in the adrenal gland and increased faster than the rate of growth during the initial rapid growth phase--the first 7 days after STZ was given; PPRibP synthetase showed a parallel increase. Formation of R5P via the oxidative and nonoxidative segments of the PPP also was measured. The oxidative enzymes, G-6-PD and 6-PGD, increased in parallel with growth during the early phase, but showed a more marked rise during the secondary, slower, growth phase seen 6 wk after STZ was given, when this may be associated with the known sustained rise in plasma corticosteroids. The nonoxidative enzymes of the PPP, an alternate route for the production of R5P, showed smaller changes. The specifically high adrenal concentration of PPRibP may be related to the high Km for PPRibP (250 microM) of the first enzyme of the de novo pathway of Pur synthesis, as such synthesis may be required in the rat to replace the net loss of ATP associated with catecholamine secretion. Factors controlling PPRibP synthetase and their potential relative importance in the adrenal gland have been considered.
Diabetes 1992 Nov
PMID:Phosphoribosyl pyrophosphate formation in the rat adrenal gland in relation to adrenal growth in experimental diabetes. 138 69

This work explored the role of the cholinergic pathway, assessed at a post-synaptic level by the use of isolated smooth muscle cells, in the impairment of antral motility associated with diabetic gastroparesis. Contractile response to carbachol--but not to erythromycin, a motilin receptor agonist--was abolished in antral smooth muscle cells isolated from (i) rats previously rendered diabetic by a single i.v. dose of streptozotocin (STZ, 60 mg/kg) and (ii) db/db spontaneously diabetic mice. Insulin treatment of STZ-rats was able to prevent the impairment of the carbachol contractile response, but not to reverse it once established. In STZ-rats, impairment of contractile response was not associated with a change in density of [3H]-N-methyl-scopolamine ([3H]-NMS) binding sites (approximately 1.5 fmol/mg protein). Displacement curve of the [3H]-NMS binding by carbachol was shifted to the right in diabetic rats as compared to controls. The addition of GTP-gamma-S induced a shift to the right of the displacement curve in control but not in diabetic animals. These results strongly suggest that diabetes is associated with an early and specific alteration of the muscarinic control of contraction of antral smooth muscles at a post-synaptic level, associated with an alteration of the GTP-binding proteins coupled to muscarinic receptors.
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PMID:Impairment of contractile response to carbachol and muscarinic receptor coupling in gastric antral smooth muscle cells isolated from diabetic streptozotocin-treated rats and db/db mice. 138 42

The etiology of the low renin state in DM is not clear. To assess the role of certain growth and regulatory factors in this process, we studied the effects of insulin, IGF-I, and IGF-II on the renin-angiotensin system in normal and 8-wk STZ-induced diabetic rats. Renin secretion was studied both in static incubations and by perifusion of rat renal cortical slices. In diabetic rats, both plasma renin activity (0.65 +/- 1.6 vs. 4.0 +/- 1.2 ng ANG I.ml-1.h-1) and tissue renin concentrations (27 +/- 5 vs. 51 +/- 8 ng ANG I.mg tissue-1.h-1) were reduced. Insulin (0.1-1.0 mu/ml) and IGF-I (10(-9) to 4 x 10(-9) M) stimulated renin secretion in normal tissue (control, 95 +/- 3%; insulin [0.5 mu/ml], 134 +/- 7%; IGF-I [4 x 10(-9) M], 149 +/- 7%). IGF-I stimulated renin secretion in perifusions as early as 30 min, whereas IGF-II had no effect. However, in diabetic renal tissue, neither insulin (0.1-1.0 mu/ml) nor IGF-I (10(-9) to 4 x 10(-9) M) had an effect on renin. This lack of effect was overcome by adding up to 100-fold higher concentrations of these growth factors. ANG II (10(-10) M-10(-8) M) had an exaggerated inhibitory effect on renin secretion in diabetic tissue. This study suggests that the low renin state in DM may be explained by the enhanced inhibitory effect of ANG II and the resistance to the secretogogue actions of insulin and IGF-I.
Diabetes 1992 Sep
PMID:Altered regulation of renin secretion by insulinlike growth factors and angiotensin II in diabetic rats. 138 18

In rats with STZ-induced diabetes mellitus, a reduction in insulin secretion is associated with increased insulin binding in the liver, muscle, fat, and kidney, but not in the brain. To test the hypothesis that tissue-specific modulation of insulin receptors (IRs) in STZ-induced diabetes occurs at the level of mRNA, IR mRNA levels were measured in the liver, kidney, and brain of Sprague-Dawley rats 15 days after intravenous administration of STZ (60 mg/kg body weight) and compared with those of control rats. Diabetic rats were either left untreated or given differing insulin regimens that were designed to achieve varying degrees of metabolic control. IR mRNA levels were measured by slot blot hybridization with a 32P-labeled rIR probe and standardized by 28S ribosomal RNA determination. Hepatic IR mRNA levels were increased significantly in both untreated diabetic rats and in those that received low-dose (2 U/day) insulin therapy. In contrast, hepatic IR mRNA levels did not differ significantly from controls in those that received moderate doses of insulin (3-8 U/day) and were significantly less than controls in those that received the highest doses (6-10 U/day). Renal IR mRNA levels also were increased significantly in the untreated diabetic rats but not in those that received low- or moderate-dose insulin therapy, and were significantly less than controls in those that received the highest doses.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1992 Sep
PMID:Tissue-specific regulation of insulin receptor mRNA levels in rats with STZ-induced diabetes mellitus. 138 19

Taurine is a cerebral osmolyte whose intracellular content changes in parallel with plasma osmolality. We conducted experiments to assess whether cerebral taurine transport is modified during chronic hyperglycemia. Rats with STZ-induced diabetes were studied after 1 wk of sustained hyperglycemia. Cerebral taurine uptake in synaptosomes (metabolically active nerve terminal vesicles) was measured using a rapid filtration technique. The synaptosomes were isolated by homogenization of the brain and purification on discontinuous Ficoll gradients (n = 8 synaptosome preparations). Diabetic rats (n = 13) displayed a 15-25% increase in synaptosomal taurine uptake compared with normoglycemic control animals (n = 12) at all time points assayed between 5 and 120 min. Thus, after a 30-min incubation, cerebral taurine uptake increased from a control level of 3.53 +/- 0.23 to 4.10 +/- 0.24 mumol/mg protein (n = 10) in hyperglycemic rats, P less than 0.03. The magnitude of the plasma-to-brain cell taurine gradient was unchanged in diabetic animals. The intrasynaptosomal taurine concentration (approximately 2 microM) and taurine efflux from the synaptosomes were no different in hyperglycemic versus control rats; efflux amounted to less than 2.5% of the uptake value at corresponding time points. Maximal brain taurine uptake under both control and experimental hyperglycemic conditions required the presence of external Na+ and Cl-. Synaptosomal taurine transport was reduced by competing beta-amino acids such as beta-alanine, beta-aminoisobutyric acid, and hypotaurine (P less than 0.01). Addition of oubain and the anionic binding site inhibitors, 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid and 4,4'diisothio-cyanatostilbene-2,2'-disulfonic acid, also decreased cerebral taurine uptake under normoglycemic and hyperglycemic conditions (P less than 0.01). The increased synaptosomal taurine uptake by diabetic rats was not a result of generalized membrane dysfunction because glycine transport was not elevated in hyperglycemic rats. The enhanced transport rate was attributable to a 35 and 81% increase in the Vmax of the high- and low-affinity taurine transporters, respectively (P less than 0.01), without significant change in the Km of the carrier systems. Treatment of hyperglycemic rats (n = 5) with ultra-long-acting insulin to normalize the serum glucose concentration restored synaptosomal taurine uptake to the level observed in normoglycemic controls. The effect of insulin was attributable to correction of hyperglycemia, because addition of insulin (500 mU/ml) to the in vitro assay system did not alter synaptosomal taurine uptake.(ABSTRACT TRUNCATED AT 400 WORDS)
Diabetes 1992 Sep
PMID:Cerebral taurine transport is increased during streptozocin-induced diabetes in rats. 138 21

The NSTZ rat model combines loss of glucose-induced insulin secretion with a reduced amount of the high Km B-cell glucose transporter, GLUT2. The purpose of this study was to determine whether the restoration of glucose-induced insulin secretion was paralleled by an increase of GLUT2. Rats injected at 2 days of age with 90 mg/kg STZ were studied at 8-13 wk of age. Insulin secretion was assessed in the isolated perfused pancreas with 16.7 mM glucose preceded by 40 min of 0 or 5.5 mM glucose. In control rats, 16.7 mM glucose caused the same large biphasic insulin response whether preceded by 0 or 5.5 mM glucose. In NSTZ rats, after 5.5 mM glucose, 16.7 mM glucose elicited virtually no rise in insulin release. In contrast, after 0 mM glucose, a large insulin response to the glucose challenge occurred that was equal to that of the control groups when the differences in B-cell mass were taken into account. However, the dose-response curve for glucose-induced insulin secretion was shifted to the left, and no second phase of insulin secretion was observed. GLUT2 was assessed after the perfusions by indirect immunofluorescence with anti-GLUT2 antisera. Both control groups showed homogenous staining in all B-cells. NSTZ rats perfused with 5.5 mM glucose had a marked diminution in GLUT2 staining. We observed no increase in GLUT2 staining in the NSTZ rats perfused with 0 mM glucose.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1992 Oct
PMID:Recovery of glucose-induced insulin secretion in a rat model of NIDDM is not accompanied by return of the B-cell GLUT2 glucose transporter. 139 6

The effect of acute streptozotocin-induced diabetes mellitus on the systemic hemodynamic parameters was studied in conscious rats by thermodilution technique. Male Wistar rats were made diabetic with a single intravenous injection of streptozotocin (STZ, 50 mg/kg). The most important finding of this work was the elucidation of the systemic vasodilation and increased cardiac index one day after STZ injection. Such alteration in hemodynamic parameters could result in the increased blood flow and capillary hypertension in some vascular beds and, therefore, be considered as a pathogenic factor in the development of diabetic microangiopathy.
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PMID:[Parameters of systemic hemodynamics in conscious rats with acute streptozotocin diabetes]. 142 Dec 17

We investigated the effects of selenium (Se) on the serum glucose and insulin levels in rats with diabetes induced by streptozotocin (STZ, 75 mg/kg, i.p.) and pancreatectomized rats. Moreover, the direct action of Se on insulin release from the isolated pancreatic islets using a slight diabetic rat was studied. The following results were obtained: 1) Selenite at a dose of 173 micrograms/kg (78.9 micrograms/kg of Se base equivalent) drastically reduced the very high level of serum glucose in acute diabetic rats within 5 to 30 min after treatment. During this time period, the insulin level in the serum showed an increasing tendency. 2) The high serum glucose level in chronic diabetic rats returned to the original level with injection of selenite for 4 days, once a day. However, Se did not elicit a significant increase in serum insulin level. 3) Although there was a tendency for the serum glucose level to decrease when selenite was administered into pancreatectomized rats, no secretion of insulin into the serum was observed. 4) Insulin release from isolated pancreatic islets was dose-dependently accelerated by the addition of selenite. These data present the new finding that Se reduced the high level of serum glucose in diabetic rats.
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PMID:[Effects of selenium on the serum glucose and insulin levels in diabetic rats]. 142 98

Untreated insulin-deficient diabetes causes hyperphagia and neuroendocrine disturbances that may be partly mediated by increased hypothalamic activity of neuropeptide Y (NPY), a potent central appetite stimulant. The metabolic signal that stimulates hypothalamic NPY is unknown. This study aimed to determine whether insulin deficiency or hyperglycemia was responsible. Regional hypothalamic NPY concentrations were compared in streptozocin-diabetic (STZ-D) rats rendered nearly normoglycemic by either insulin replacement or food restriction. Untreated STZ-D rats were hyperphagic and showed significantly increased (p less than 0.01) hypothalamic NPY concentrations in the arcuate nucleus and lateral hypothalamic area. Once-daily ultralente insulin injections corrected hypoinsulinemia and hyperglycemia, abolished hyperphagia, and normalized NPY concentrations in all hypothalamic regions. By contrast, food restriction effectively lowered glycemia without raising insulin levels. In these underfed diabetic rats, NPY concentrations rose further and were significantly higher than nondiabetic and untreated diabetic levels in most hypothalamic regions. We conclude that insulin deficiency is a major stimulus to hypothalamic NPY in STZ-D, whereas hyperglycemia may exert an inhibitory influence. These findings support the hypothesis that hypothalamic NPY responds to specific metabolic cues and is involved in regulating energy balance and conserving body weight.
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PMID:Insulin deficiency is a specific stimulus to hypothalamic neuropeptide Y: a comparison of the effects of insulin replacement and food restriction in streptozocin-diabetic rats. 143 14


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