Assessment of the antidiabetic activity of epicatechin in streptozotocin-diabetic and spontaneously diabetic BB/E rats

1985 ◽  
Vol 5 (3) ◽  
pp. 215-221 ◽  
Author(s):  
A. J. bone ◽  
C. S. T. Hii ◽  
D. Brown ◽  
W. Smith ◽  
S. L. Howell

(−)-Epicatechin has previously been suggested to rapidly reverse alloxan diabetes in rats. We have assessed the therapeutic value of the compound in two further animal models of insulin-dependent diabetes mellitus, namely streptozotocin – diabetic rats and the spontaneously diabetic BB/E rat. There was no indication of a reversal of established diabetes in either the streptozotocin-diabetic or the spontaneously diabetic BB/E rats. Moreover, epicatechin also failed to halt the progression of the disease in prediabetic BB/E rats. Earlier claims of the potential use of epicatechin as an antidiabetic agent must therefore be treated with some caution.

1995 ◽  
Vol 268 (6) ◽  
pp. H2366-H2374 ◽  
Author(s):  
H. G. Bohlen ◽  
J. M. Lash

Alterations in the structural properties of the microvasculature and in vasodilation mediated by endothelial- and, to some extent, nonendothelial-dependent mechanisms occurs in insulin-dependent diabetic humans and animals. Less severe problems of this type appear to occur during non-insulin-dependent diabetes mellitus (NIDDM) in humans, but data based on animal models of NIDDM are not available. The endothelial- and nonendothelial-mediated dilation of intestinal arterioles was studied in insulin-resistant male Zucker fatty diabetic (DB) rats and their lean normal male littermates (LM) at ages 22-25 and 35-40 wk. DB become hyperglycemic (450-550 mg/100 ml) at age 9-10 wk. Microiontophoretic release of acetylcholine, ADP, and nitroprusside onto arterioles caused equivalent dilation in LM and DB for both large and intermediate diameter arterioles. Administration of streptozotocin (STZ) to DB at age 18-19 wk lowered their insulin concentration approximately 25% but did not significantly effect the resting plasma glucose concentration. However, endothelial-dependent vasodilation was attenuated by 70-80% within 8-10 wk. The overall results indicate that prolonged hyperglycemia in insulin-resistant but hyperinsulinemic rats does not impair the endothelial- and nonendothelial-dependent dilation of the intestinal microvasculature. However, compromising beta-cell function with STZ, as indicated by lowering the insulin concentration by one-fourth, substantially compromises endothelial-dependent dilation similar to that found in insulin-dependent diabetic rats and humans.


1987 ◽  
Vol 252 (1) ◽  
pp. E13-E20 ◽  
Author(s):  
N. Bank ◽  
M. A. Lahorra ◽  
H. S. Aynedjian

We examined the effect of calcium administration on renal hyperfiltration in streptozotocin-treated diabetic rats. Rats were studied 7–10 days after streptozotocin injection. Intrarenal infusion of CaSO4 in Ringer's solution had no effect on the hyperfiltration of the diabetic kidney. Infusion of insulin in a dose that did not effect hyperglycemia also had no effect on the hyperfiltration. However, when insulin and calcium were infused together, a rapid decrease in glomerular filtration rate, single-nephron filtration rate, glomerular hydraulic pressure, and renal plasma flow occurred. The contralateral control kidney was unaffected. Verapamil infusion had no significant effect in untreated diabetic rats, but immediately reversed the vasoconstriction induced by insulin plus calcium. Similar intrarenal insulin and calcium infusions had no effect in euvolemic or chronically salt-loaded nondiabetic rats. The observations indicate that renal vascular cells (probably preglomerular) are hyperresponsive to calcium in early insulin-dependent diabetes mellitus and that this response requires insulin. We suggest that decreased renal vascular tone in early insulin-dependent diabetes mellitus may be due in part to defective transmembrane calcium flux across vascular smooth muscle cells. Insulin appears to be required for calcium entry or mobilization, to initiate renal vascular smooth muscle contraction in diabetes.


1997 ◽  
Vol 273 (4) ◽  
pp. H1888-H1893 ◽  
Author(s):  
Kristine K. Hicks ◽  
Ernst Seifen ◽  
Joseph R. Stimers ◽  
Richard H. Kennedy

Experiments were designed to determine whether insulin-dependent diabetes mellitus (IDDM) alters direct chronotropic effects of adrenergic and cholinergic agonists and whether the observed changes are associated with hyperglycemia or combined hyperglycemia and ketoacidosis. Diabetes was induced by intravenous administration of 45, 50, or 65 mg/kg streptozotocin (STZ). Rats treated with 65 mg/kg STZ had higher levels of blood glucose and ketones compared with the levels of the other groups. Right atria were isolated 12 wk after administration of STZ and bathed in Krebs-Henseleit solution. Basal spontaneous pacemaker rate was diminished in preparations isolated from diabetic rats. The maximum pacemaker rate observed during exposure to isoproterenol or norepinephrine was also depressed in preparations from diabetic animals; however, the increase in rate and half-maximal effective concentration values for each agent were not affected. The sensitivity to the negative chronotropic action of acetylcholine was enhanced by IDDM, whereas the response to carbachol (a cholinergic agonist not readily metabolized by acetylcholinesterase) was not changed. No significant differences were observed when we compared preparations isolated from diabetic animals with and without ketoacidosis. In summary, these data suggest 1) that IDDM is associated with a diminished basal spontaneous pacemaker without changes in the responsiveness to adrenergic and cholinergic receptor activation and 2) that ketoacidosis does not play a role in the observed alterations.


1996 ◽  
Vol 271 (1) ◽  
pp. H192-H202 ◽  
Author(s):  
C. E. Flarsheim ◽  
I. L. Grupp ◽  
M. A. Matlib

The objective of this study was to determine whether a defect in mitochondrial respiratory function accompanies the development of diabetic cardiomyopathy. The hypothesis tested in this study is that a decrease in Ca2+ uptake into mitochondria may prevent the stimulation of Ca(2+)-sensitive matrix dehydrogenases and the rate of ATP synthesis. Streptozotocin (55 mg/kg)-induced diabetic rats were used as a model of insulin-dependent diabetes mellitus. Hearts from 4-wk diabetic rats had basal heart rates and rates of contraction and relaxation similar to control. Isoproterenol caused a similar increase in the rate of contraction in diabetic and control hearts, whereas the peak rate of relaxation was reduced in diabetic hearts. Mitochondrial Ca2+ uptake was reduced in mitochondria from diabetic hearts after 2 wk of diabetes. Na(+)-induced Ca2+ release was unchanged. State 3 respiration rate was depressed in mitochondria from diabetic rats only when the respiration was supported by the substrate of a Ca(2+)-regulated matrix enzyme. The pyruvate dehydrogenase activity was reduced in diabetic mitochondria compared with that of control. It was concluded that mitochondria from diabetic hearts had a decreased capacity to upregulate ATP synthesis via stimulation of Ca(2+)-sensitive matrix dehydrogenases. The impairment in the augmentation of ATP synthesis rate accompanies a decreased rate of relaxation during increased work load.


2003 ◽  
Vol 82 (4) ◽  
pp. 322-325 ◽  
Author(s):  
A. Iwama ◽  
N. Nishigaki ◽  
K. Nakamura ◽  
I. Imaizumi ◽  
N. Shibata ◽  
...  

Diabetes mellitus is associated with depression of natural defenses against infection and increases the risk of periodontal disease. However, the effects of diabetes on periradicular tissue, which differs structurally from periodontal tissue, are not known. In this study, we evaluated the effects of type 2 diabetes on the development of periradicular lesions after exposure of the pulp in the left mandibular first molar through the occlusal surface in rats. GK rats with spontaneous non-insulin-dependent diabetes mellitus and Wistar rats (controls) received a normal laboratory diet and either water or a 30% sucrose solution. At both 2 and 4 weeks after pulp exposure, histologic analysis showed that alveolar bone resorption was most severe and the periradicular lesions were largest in diabetic rats given the sucrose solution. These results suggest that the metabolic conditions produced by type 2 diabetes enhance the development of periradicular lesions in rats.


2010 ◽  
Vol 29 (10) ◽  
pp. 865-871 ◽  
Author(s):  
Mohamed Bnouham ◽  
Fatima Zahra Merhfour ◽  
Abderrahim Ziyyat ◽  
Mohamed Aziz ◽  
Abdelkhaleq Legssyer ◽  
...  

The goal of the present study is to test the effect of water extract (WE) of four medicinal plants used as antidiabetics in Eastern Morocco (Arbutus unedo: Au, Ammoïdes pusilla: Ap, Thymelaea hirsuta: Th, and Urtica dioïca: Ud). These plants are used in cooking to bring out the flavor in a dish or to complement it. The first experiment was realized in order to determine the antidiabetic effect of the WE of these plants during 5 weeks’ treatment. Seven groups of Wistar rats were used: Healthy controls, neonatal streptozotocin (n-stz) induced-diabetic rats (90 mg/kg; intraperitoneally [i.p.]), n-stz + tolbutamide (400 mg/l), and 4 groups n-stz + WE of plants (400 mg/l, drink water). The percentages of Plasma glucose lowering effect were, respectively for Au, Ap, Th, Ud and tolbutamide: 31.6 % p<0.01, 27.4 % p<0.05, 38.2 % p<0.01, 13 % and 33.9 % p<0.05 when compared with untreated diabetic controls. In a second experiment, oral glucose tolerance tests were carried out in n-stz induced-diabetic rats. The i.p. administration of the water extract (WE) of Ap and Ud (150 mg/kg) 30 minutes before the glucose overload (2 g/kg) showed a significant reduction glycemia, respectively of 36 % at 60 min (p<0.05) and 50 % at 180 min (p<0.05) after glucose overload compared with controls. In contrast, the effect of WE of Au and Th (150 mg/kg, i.p.) was not significant. The in vitro study of glucose utilization by isolated rat hemidiaphragm suggests that these extracts in combination with insulin potentiate its activity and enhance the utilization of glucose. In conclusion, it seems that these plants possess antidiabetic activity.


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