Possible role of corticosterone in the down-regulation of the hypothalamo-hypophysial-thyroid axis in streptozotocin-induced diabetes mellitus in rats

1997 ◽  
Vol 153 (2) ◽  
pp. 259-267 ◽  
Author(s):  
G A C van Haasteren ◽  
E Sleddens-Linkels ◽  
H van Toor ◽  
W Klootwijk ◽  
F H de Jong ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Median Eminence ◽  
Plasma Corticosterone ◽  
Diabetic Rats ◽  
Type I ◽  
Thyroid Axis ◽  
Streptozotocin Induced Diabetes ◽  
The Difference

Abstract We investigated the effects of diabetes mellitus on the hypothalamo-hypophysial-thyroid axis in male (R×U) F1 and R-Amsterdam rats, which were found to respond to streptozotocin (STZ)-induced diabetes mellitus with no or marked increases, respectively, in plasma corticosterone. Males received STZ (65 mg/kg i.v.) or vehicle, and were killed 1, 2 or 3 weeks later. At all times studied, STZ-induced diabetes mellitus resulted in reduced plasma TSH, thyroxine (T4) and 3,5,3′-tri-iodothyronine (T3). Since the dialyzable T4 fraction increased after STZ, probably as a result of decreased T4-binding prealbumin, plasma free T4 was not altered during diabetes. In contrast, both free T3 and its dialyzable fraction decreased during diabetes, which was associated with an increase in T4-binding globulin. Hepatic activity of type I deiodinase decreased and T4 UDP-glucuronyltransferase increased after STZ treatment. Thus, the lowered plasma T3 during diabetes may be due to decreased hepatic T4 to T3 conversion. Median eminence content of TRH increased after STZ, suggesting that hypothalamic TRH release is reduced during diabetes and that this is not caused by impaired synthesis or axonal transport of TRH to the median eminence. Hypothalamic proTRH mRNA did not change in diabetic (R×U) F1 rats during the period of observation, but was lower in R-Amsterdam rats 3 weeks after STZ. Similarly, pituitary TSH and TSHβ mRNA had decreased in R-Amsterdam rats by 1 week after STZ treatment, but did not change in (R×U) F1 rats. The difference between the responses in diabetic R-Amsterdam and (R×U) F1 rats may be explained on the basis of plasma corticosterone levels which increased in R-Amsterdam rats only. Hypothalamic TRH content was not affected by diabetes mellitus, but the hypothalami of diabetic rats released less TRH in vitro than those of control rats. Moreover, insulin had a positive effect on TRH release in vitro. In conclusion, the reduced hypothalamic TRH release during diabetes is probably not caused by decreases in TRH synthesis or transport to the median eminence, but seems to be due to impaired TRH release from the median eminence which may be related to the lack of insulin. Inhibition of proTRH and TSHβ gene expression in diabetic R-Amsterdam rats is not a primary event but appears to be secondary to enhanced adrenal activity in these animals during diabetes. Journal of Endocrinology (1997) 153, 259–267

scholarly journals The role of nicotinamide in the correction of renal function in diabetic nephropathy

2019 ◽  
Vol 23 (2) ◽  
pp. 218-221
Author(s):  
L. V. Yanitskaya ◽  
L. F. Osinskaya ◽  
A. V. Redko
Keyword(s):  
Diabetes Mellitus ◽  
Body Weight ◽  
Diabetic Nephropathy ◽  
Statistical Analysis ◽  
Rat Kidney ◽  
Clinical Manifestations ◽  
Diabetic Rats ◽  
Cortical Layer ◽  
The Difference

Hyperglycemia of diabetes mellitus leads to the activation of the polyol way of oxidation of glucose with the activation of the enzymes of aldose reductase and sorbitol dehydrogenase and of their coenzymes NADPH and NAD, which triggers the mechanism of formation of sorbitol. The consequences of these changes lead to microangiopathy of the tissues of the kidneys, which may be one of the pathogenetic mechanisms of diabetic nephropathy. In an accessible literature, the role of coenzymes of sorbitol pathway in the development of diabetic nephropathy is not sufficiently defined. The purpose of the study was to study the content of NAD and NADPH coenzymes, their correlation, and their role in the mechanism of kidney damage in diabetes mellitus and to predict the possible correction of these changes with the NAD-nicotinamide derivative. The study was conducted on a model of streptotrozectinic diabetes mellitus (single administration of streptozotocin in a dose of 60 mg per 1 kg of body weight). Four weeks after induction of diabetes, nicotinamide (100 mg per 1 kg body weight) was injected. The level of glucose was determined by the Accu-chek (Roshe Diagnostics, Switzerland) glucose meter. The content of NAD and NADH was determined in the non-protein extracts. The statistical analysis was carried out using the Microsoft Excel statistical analysis program. The difference between the indicators was considered statistically significant (p<0.05). The NAD level was reduced by 31%, the NAD/NADN ratio was 32%. The dependence of the ratio of NADP/NADPN in conditions of hyperglycemia of diabetes mellitus with clinical manifestations of diabetic nephropathy is determined. A decrease in the ratio of NADP/NADPN to 38% in the rat kidney in the cortical layer was detected. The introduction of nicotinamide normalized the reduced content of NAD diabetic rats. These results provide perspectives for further research in which nicotinamide can be used as a renal protector.

Role of vasopressin in diabetes mellitus-induced changes in medullary transport proteins involved in urine concentration in Brattleboro rats

2004 ◽  
Vol 286 (4) ◽  
pp. F760-F766 ◽  
Author(s):  
Dongun Kim ◽  
Jeff M. Sands ◽  
Janet D. Klein
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Rats ◽  
Urine Concentration ◽  
Transport Proteins ◽  
Protein Abundance ◽  
Brattleboro Rats ◽  
Urea Transporter ◽  
Streptozotocin Induced Diabetes ◽  
Induced Changes

In rats with streptozotocin-induced diabetes mellitus for 10–20 days, we showed that the abundance of the major medullary transport proteins involved in the urinary concentrating mechanism, urea transporter (UT-A1), aquaporin-2 (AQP2), and the Na+-K+-2Cl- cotransporter (NKCC2/BSC1), is increased, despite the ongoing osmotic diuresis. To test whether vasopressin is necessary for these diabetes mellitus-induced changes in UT-A1, AQP2, or NKCC2/BSC1, we studied Brattleboro rats because they lack vasopressin. Brattleboro rats were given vasopressin (2.4 μg/day via osmotic minipump) for 5 or 12 days. At 5 days, vasopressin increased AQP2 protein abundance but decreased UT-A1 abundance compared with untreated Brattleboro rats. At 12 days, vasopressin increased the abundance of both UT-A1 and AQP2 proteins but did not alter NKCC2/BSC1. Next, untreated Brattleboro rats were made diabetic for 10 days by injecting them with streptozotocin (40 mg/kg). Diabetes mellitus increased the abundance of AQP2 and NKCC2/BSC1 proteins, but UT-A1 protein abundance did not increase. Third, vasopressin-treated Brattleboro rats were made diabetic with streptozotocin for 10 days. In vasopressin-treated Brattleboro rats, diabetes mellitus increased UT-A1, AQP2, and NKCC2/BSC1 protein abundances. Vasopressin significantly increased UT-A1 phosphorylation in vasopressin-treated diabetic Brattleboro rats but not in the other groups of Brattleboro rats. We conclude that 1) administering vasopressin to Brattleboro rats for 12 days, but not for 5 days, increases UT-A1 protein abundance and 2) vasopressin is necessary for the increase in UT-A1 protein in diabetic rats but is not necessary for the increase in AQP2 or NKCC2 proteins.

scholarly journals In vivo correlation of olive leaves extract on some oxidative stress markers in streptozotocin-induced diabetes mellitus in rats

2018 ◽  
Vol 69 (1) ◽  
pp. 243 ◽  
Author(s):  
A. M.R. Afify ◽  
H. S. El-Beltagi ◽  
S. A. Fayed ◽  
A. E. El-Ansary
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Diabetic Control ◽  
Diabetic Rats ◽  
Adult Rats ◽  
Male Adult ◽  
Stress Markers ◽  
Streptozotocin Induced Diabetes

Diabetes mellitus type two (T2DM) is one of the most extensive diseases in the world. Herbal therapy remains a possible adjunct therapy to sustain better glycemic control and reduce complications arising from diabetes. In order to evaluate the curative impacts of olive leaf extract (OLE) on streptozotocin (STZ)-induced diabetic rats, twenty-four Wistar male adult rats were divided into four equal groups; control, diabetic control (45 mg/kg STZ), normal rats treated with OLE (17.8 mg/kg b.wt.), and diabetic rats treated with OLE (45 mg/kg STZ + 17.8 mg/kg b.wt.). The OLE extract was investigated for in vitro antioxidant activity using the DPPH• assay. The phenolic, tannin, and flavonoid contents were determined. The activity of GPX, SOD, and GSH in RBC lysate, CAT in plasma and MDA in serum were measured. The OLE prevented the decrease in GSH and kept MDA around the normal range in the treated diabetic rats. The current study suggests that OLE might be used safely to ameliorate T2DM and its accompanying oxidative stress.

scholarly journals Role of nitric oxide and angiotensin II in diabetes mellitus-induced glomerular hyperfiltration.

1996 ◽  
Vol 7 (1) ◽  
pp. 105-112 ◽  
Author(s):  
K M Mathis ◽  
R O Banks
Keyword(s):  
Nitric Oxide ◽  
Diabetes Mellitus ◽  
Angiotensin Ii ◽  
Diabetic Rats ◽  
Constant Infusion ◽  
Systemic Response ◽  
Vasoactive Factors ◽  
Streptozotocin Induced Diabetes ◽  
Intact Rats

The goal of this study was to determine what extent nitric oxide (NO) and/or angiotensin II (AngII) are involved in the hyperfiltration observed in rats with streptozotocin-induced diabetes mellitus. Studies were performed on anesthetized rats 7 to 10 days after the induction of diabetes. Nitro-L-arginine (LNA) was used to inhibit NO synthesis, and losartan was used to block AngII receptors. Three protocols were utilized: (i) control and diabetic rats treated with a constant infusion of LNA; (ii) control and diabetic rats treated first with a constant infusion of losartan and then LNA plus losartan; and (iii) nephrectomized control and diabetic rats treated with LNA (to evaluate the involvement of renal vasoactive factors other than AngII in the systemic response to LNA). Compared with controls, diabetics had a significantly elevated baseline GFR but the same mean arterial pressure (MAP). In Protocol i, LNA caused the same increase in MAP in both groups but only decreased the GFR in controls. In Protocol ii, losartan caused a significant increase in the GFR only in controls. The coinfusion of LNA and losartan caused no change in the GFR in controls but induced a large GFR decrease in diabetics. Losartan had no effect on MAP in either group and did not affect the LNA-induced increase in MAP in either group. The LNA-induced increase in MAP was greater in nephrectomized rats compared with that in intact rats. These data indicate that (1) neither changes in the synthesis of NO nor changes in the actions of AngII, alone, are responsible for the hyperfiltration observed in streptozotocin-induced diabetes; (2) a combined alteration in these two systems may account for diabetes-induced hyperfiltration; (3) the LNA-induced decrease in GFR in control but not in diabetic rats is an AngII-mediated event; and (4) AngII is not involved in the LNA-induced increase in MAP in either control or diabetic rats but other renal factors cannot be ruled out in this response.

scholarly journals Characterization of N-glycosylated type I collagen in streptozotocin-induced diabetes

1981 ◽  
Vol 197 (2) ◽  
pp. 405-412 ◽  
Author(s):  
A Le Pape ◽  
J P Muh ◽  
A J Bailey
Keyword(s):  
Type I Collagen ◽  
Accelerated Aging ◽  
Diabetic Rats ◽  
Type I ◽  
Significant Extent ◽  
Streptozotocin Induced Diabetes ◽  
Cross Links ◽  
The Stability

The N epsilon-glycosylation of lysine and hydroxylysine residues in collagen from streptozotocin-induced-diabetic rats was confirmed and the stability of the complex shown to be due to an Amadori rearrangement. The studies also demonstrate the relative specificities of glucose, galactose and mannose in their reaction with collagen. The glycosylation of lysine in vitro occurs with glucose and galactose, but not with mannose, whereas only gucose reacts with hydroxylysine to any significant extent. Glycosylation of collagen occurs slowly during normal aging, but in contrast with reports suggesting accelerated aging of collagen in diabetic animals, we clearly demonstrated that the apparent increased stability is not due to an acceleration of the normal maturation process involving the reducible cross-links.

On the Role of Transferrin in 67Ga Uptake by Tumor Cells

1988 ◽  
Vol 27 (04) ◽  
pp. 151-153
Author(s):  
P. Thouvenot ◽  
F. Brunotte ◽  
J. Robert ◽  
L. J. Anghileri
Keyword(s):  
Specific Binding ◽  
Subcellular Fractionation ◽  
Animal Blood ◽  
Tumor Bearing ◽  
Cell Structures ◽  
The Difference ◽  
Sarcoma Cells ◽  
In Vitro Uptake

In vitro uptake of 67Ga-citrate and 59Fe-citrate by DS sarcoma cells in the presence of tumor-bearing animal blood plasma showed a dramatic inhibition of both 67Ga and 59Fe uptakes: about ii/io of 67Ga and 1/5o of the 59Fe are taken up by the cells. Subcellular fractionation appears to indicate no specific binding to cell structures, and the difference of binding seems to be related to the transferrin chelation and transmembrane transport differences

Ciamexon in low-dose streptozotocin induced diabetes mellitus. In vivo and in vitro studies

1986 ◽  
Vol 113 (1_Suppl) ◽  
pp. S120-S121
Author(s):  
TH. LINN ◽  
H. GERMANN ◽  
B. HERING ◽  
R. BRETZEL ◽  
K. FEDERLIN
Keyword(s):  
Diabetes Mellitus ◽  
Low Dose ◽  
In Vitro Studies ◽  
Streptozotocin Induced Diabetes

scholarly journals Nociceptin Increases Antioxidant Expression in the Kidney, Liver and Brain of Diabetic Rats

Biology ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 621
Author(s):  
Ernest Adeghate ◽  
Crystal M. D’Souza ◽  
Zulqarnain Saeed ◽  
Saeeda Al Jaberi ◽  
Saeed Tariq ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Rats ◽  
Enzyme Linked Immunosorbent Assay ◽  
Kidney Tubules ◽  
Onset Of Diabetes ◽  
Endogenous Antioxidants ◽  
Kidney Liver ◽  
Convoluted Tubules ◽  
The Brain

Nociceptin (NC) consists of 17 amino acids (aa) and takes part in the processing of learning and memory. The role of NC in the induction of endogenous antioxidants in still unclear. We examined the effect of NC on the expression of endogenous antioxidants in kidney, liver, cerebral cortex (CC), and hippocampus after the onset of diabetes mellitus, using enzyme-linked immunosorbent assay and immunohistochemistry. Exogenous NC (aa chain 1–17; 10 µg/kg body weight) was given intraperitoneally to normal and diabetic rats for 5 days. Our results showed that catalase (CAT) is present in the proximal (PCT) and distal (DCT) convoluted tubules of kidney, hepatocytes, and neurons of CC and hippocampus. The expression of CAT was significantly (p < 0.05) reduced in the kidney of normal and diabetic rats after treatment with NC. However, NC markedly (p < 0.001) increased the expression CAT in the liver and neurons of CC of diabetic rats. Superoxide dismutase (SOD) is widely distributed in the PCT and DCT of kidney, hepatocytes, and neurons of CC and hippocampus. NC significantly (p < 0.001) increased the expression of SOD in hepatocytes and neurons of CC and the hippocampus but not in the kidney. Glutathione reductase (GRED) was observed in kidney tubules, hepatocytes and neurons of the brain. NC markedly increased (p < 0.001) the expression of GRED in PCT and DCT cells of the kidney and hepatocytes of liver and neurons of CC. In conclusion, NC is a strong inducer of CAT, SOD, and GRED expression in the kidney, liver and brain of diabetic rats.

Vasopressin V1 and V2 receptors in diabetes mellitus

1994 ◽  
Vol 266 (2) ◽  
pp. E217-E223 ◽  
Author(s):  
D. Trinder ◽  
P. A. Phillips ◽  
J. M. Stephenson ◽  
J. Risvanis ◽  
A. Aminian ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Inositol Phosphate ◽  
Free Water ◽  
Diabetic Rats ◽  
Biological Responses ◽  
Liver And Kidney ◽  
Streptozotocin Induced Diabetes ◽  
V2 Receptor ◽  
Plasma Arginine ◽  
Long Acting

Diabetes mellitus causes hypertonicity, increased plasma arginine vasopressin (AVP), polydipsia, and polyuria. Downregulation of AVP V2 receptors may contribute to the polyuria through diminished V2 receptor-mediated free water retention. After 2 wk of streptozotocin-induced diabetes mellitus, the diabetic rats had raised plasma glucose, AVP, and osmolality levels (P < 0.001) compared with nondiabetic controls (Sham). Insulin treatment (4 U long-acting insulin sc, daily) partially lowered these values (P < 0.01). There was a reduction in the number of renal and hepatic V1 receptors in the diabetic and diabetic+insulin animals compared with the sham animals (P < 0.05). The receptor affinity remained unchanged. In parallel, there was a reduction in maximum AVP-activated total inositol phosphate production in the liver and kidney of the diabetic and diabetic+insulin animals compared with the sham animals (P < 0.05). The density and affinity of renal V2 receptors and AVP-stimulated adenosine 3',5'-cyclic monophosphate production in the diabetic and diabetic+insulin animals were unchanged compared with the sham. These results demonstrate differential regulation of AVP receptors and suggest that downregulation of renal V2 receptors does not contribute to the polyuria of diabetes. In contrast, downregulation of V1 receptors might contribute to diminished V1 receptor-mediated biological responses to AVP seen in diabetes mellitus.

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