Partial preservation of pancreatic β-cells by vanadian: Evidence for long-term amelioration of diabetes

Cam, Margaret C.; Li, W.M.; McNeill, John H.

doi:10.1016/s0026-0495(97)90121-9

Cited by 40 publications

(17 citation statements)

References 42 publications

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“…There was a strong correlation between residual insulin store and fed glycemia in the D group (r¼ ¹0.93, P¼0.0003) (Fig. 5B), which was similar to our previous observations in untreated diabetic rats (6). DP animals also demonstrated a strong correlation (r¼ ¹0.88, P¼0.0007) that was distinct from D, whereas no correlation was found in DT animals.…”

Section: Pancreatic Insulin Content and Islet Histologysupporting

confidence: 89%

“…Similarly, following a high STZ dose (75 mg/kg), hyperglycemia recurred in all animals after vanadium treatment was withdrawn (40). It is notable in this study that the more responsive DT-LC animals were also ones that maintained a critical level of pancreatic insulin store (150 mU/g) previously found to support normoglycemia per se (6), and hence can be predicted to remain normal had treatment been withdrawn. Although food restriction similarly reduced plasma insulin levels throughout the entire study, the relative improvement in residual insulin store in DP animals was still less than that resulting from vanadium treatment.…”

Section: Discussionmentioning

confidence: 63%

“…Chronic vanadium treatment also reverses the diabetic state for up to 20 weeks after removal from treatment, a phenomenon associated with increased plasma insulin levels and an enhanced beta-cell mass (4,5). Consequently, we demonstrated that short-term treatment with vanadium prior to and for a short period (2 weeks) following the induction of STZ-diabetes eliminated hyperglycemia after withdrawal from treatment (6). Chronic amelioration of the diabetic state in these animals was related to a small but significant increase in the pancreatic insulin store.…”

Section: Introductionmentioning

confidence: 61%

“…DP animals also demonstrated a strong correlation (r¼ ¹0.88, P¼0.0007) that was distinct from D, whereas no correlation was found in DT animals. The level of pancreatic insulin store found within the DT-LC subgroup (>150 mU/g) is sufficient for the maintenance of normoglycemia in the absence of vanadium (6). Aldehyde-fuchsin staining revealed that the beta-cells in islets of control animals were well granulated (Fig.…”

Section: Pancreatic Insulin Content and Islet Histologymentioning

confidence: 92%

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Distinct glucose lowering and beta cell protective effects of vanadium and food restriction in streptozotocin-diabetes

Cam

Rodrigues²,

1999

European Journal of Endocrinology

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Vanadium is an oral insulin-mimetic agent that diminishes hyperglycemia, improves beta-cell insulin store and secretory function, and can reverse the diabetic state chronically after withdrawal from treatment. As food restriction has been reported to enhance insulin sensitivity and reduce insulin demand, we assessed the contribution of a reduced food intake to the glucose lowering and beta-cell protective effects of vanadium. Streptozotocin (STZ)-diabetic rats were untreated (D) or administered vanadyl sulfate in the drinking water (DT) at one week prior to and for 5 weeks following the administration of STZ. An additional group was pair-fed (DP) with an equal amount of food as that consumed by the DT group. Shortly after the induction of diabetes, hyperglycemic D rats demonstrated a significant rise in plasma insulin to levels that initially exceeded that of the controls. This was followed by a steady reduction over several weeks, suggesting a gradual depletion of functional beta-cells. Both vanadium treatment and pair-feeding abolished the insulin hypersecretory response following STZ administration. Glucose lowering was enhanced in DT animals when administered higher concentrations of vanadium, despite no further reduction in food intake, and all DT animals (10/10) were normoglycemic by 5 weeks. Mean pancreatic insulin content in DT rats was improved fourfold and was associated with a greater number of granulated beta-cells. Conversely, food restriction only modestly improved glycemia and the pancreatic insulin store and, unlike DT, DP rats remained highly glucoseintolerant. At 5 weeks of diabetes, fed circulating glucose and insulin levels were strongly correlated (P=0.0002) in the D and DP groups, supporting the notion that glucose lowering with food restriction is dependent on improved plasma insulin levels. A separate correlation was observed in DT animals within a lower range of plasma insulin, suggesting that vanadium, unlike food restriction, reduced plasma glucose by enhancing insulin sensitivity. Thus, vanadium preserves beta-cells in STZ-diabetes at least partially by abolishing the insulin hypersecretory response and the eventual exhaustion of residual insulin stores following a moderate dose of STZ. This property of vanadium would appear to be useful in the treatment of prediabetic and newly diagnosed insulin-dependent diabetes mellitus.

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Section: Pancreatic Insulin Content and Islet Histologysupporting

confidence: 89%

Section: Discussionmentioning

confidence: 63%

Section: Introductionmentioning

confidence: 61%

Section: Pancreatic Insulin Content and Islet Histologymentioning

confidence: 92%

See 2 more Smart Citations

Distinct glucose lowering and beta cell protective effects of vanadium and food restriction in streptozotocin-diabetes

Cam

Rodrigues²,

1999

European Journal of Endocrinology

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“…This would provide evidence for a regeneration of B-cells within the pancreatic islets, preservation of the cells during the progression of the disease, or functional stimulation of existing β-cells. A similar phenomenon was observed in streptozotocin-induced type I diabetic rats (Cam et al 1997(Cam et al , 2000Clark et al 2004) and attributed to functional enhancement of existing β-cells. Overall, it is likely that the TV decoction also regulates blood glucose levels by influencing the entry of glucose into the tissue through postreceptor mechanisms as well as by preserving β-cell function through insulin release from the pancreas.…”

Section: Discussionsupporting

confidence: 76%

Effective control of glycemic status and toxicity in Zucker diabetic fatty rats with an orally administered vanadate compound

Clark

Edel²,

Heyliger³

et al. 2004

Can. J. Physiol. Pharmacol.

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A novel black tea decoction containing vanadate has successfully replaced insulin in a rat model of insulindependent diabetes but is untested in non-insulin-dependent diabetic animals. A tea-vanadate decoction (TV) containing 30 or 40 mg sodium orthovanadate was administered by oral gavage to two groups of Zucker diabetic fatty rats and a conventional water vehicle containing 30 or 40 mg of sodium orthovanadate to two others. In the latter group receiving the 30-mg dose, vanadate induced diarrhea in 50% of the rats and death in 10%. In contrast, TV-treated rats had no incidence of diarrhea and no deaths. Symptoms were more severe in both groups with higher vanadate doses, so these were discontinued. After~16 weeks, the level of vanadium in plasma and tissue extracts was negligible in a further group of untreated rats but highly elevated after vanadate treatment. Vanadium levels were not significantly different between the TV-treated diabetic rats and the diabetic rats given vanadate in a water vehicle. Over the 115 days of the study, blood glucose levels increased from~17 to 25 mmol/L in untreated diabetic rats. This was effectively lowered (to <10 mmol/L) by TV treatment. Fasting blood glucose levels were 5, 7, and 20 mmol/L in control (nondiabetic, untreated), TV-treated and untreated diabetic rats, respectively. Rats required treatment with TV for only~50% of the days in the study. Increase in body mass during the study was significantly lower in untreated diabetic rats (despite higher food intake) than the other groups. Body mass gain and food intake were normal in TV-treated rats. Water intake was 28 mL/rat daily in control rats, 130 mL/rat daily in untreated diabetic rats, and 52 mL/rat daily in TV-treated diabetic rats. Plasma creatinine and aspartate aminotransferase levels were significantly depressed in untreated diabetic rats, and TV treatment normalized this. Our results demonstrate that a novel oral therapy containing black tea and vanadate possesses a striking capacity to regulate glucose and attenuates complications in a rat model of type II diabetes.Key words: diabetes mellitus, tea, glycemia, type II diabetes. 894Résumé : Une nouvelle décoction de thé noir contenant du vanadate a remplacé efficacement l'insuline dans un modèle de diabète insulinodépendant chez le rat; cette décoction n'a toutefois pas été testée chez les animaux diabétiques non insulinodépendants. La décoction de thé/vanadate (TV) (contenant 30 ou 40 mg de Na-orthovanadate) a été administrée par gavage oral à des rats obèses diabétiques Zucker (D). Le Na-orthovanadate (30 mg), administré dans un excipient aqueux classique, a provoqué une diarrhée chez 50 % des rats D et la mort chez 10 %. À l'opposé, les rats traités avec TV n'ont eu aucune incidence de diarrhée ni de mortalité. Les symptômes ont été plus graves chez les deux groupes ayant reçu les plus fortes doses de vanadate, de sorte que ces doses ont été supprimées. Après environ 16 semaines, le taux de vanadium dans les extraits de plasma et de tissu a été néglig...

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Treatment of diabetes with vanadium salts: general overview and amelioration of nutritionally induced diabetes in thePsammomys obesus gerbil

Shafrir

Spielman

Nachliel

et al. 2001

Diabetes Metab. Res. Rev.

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The model utilized in our study was Psammomys obesus (sand rat), a desert gerbil which becomes hyperglycemic and hyperinsulinemic on an ad libitum high energy (HE) diet. In contrast to the previously investigated insulin deficient models, vanadyl sulphate was used to correct insulin resistance and hyperinsulinemia, which led to beta-cell loss. Administration of 5 mg/kg vanadyl sulfate for 5 days resulted in prolonged restoration of normoglycemia and normoinsulinemia in most animals, return of glucose tolerance to normal, and a reduction of hepatic phosphoenolpyruvate carboxykinase activity. There was no change in food consumption and in regular growth during or after the vanadyl treatment. Pretreatment with vanadyl sulfate, followed by transfer to a HE diet, significantly delayed the onset of hyperglycemia. Hyperinsulinemic-euglycemic clamp of vanadyl sulfate treated Psammomys demonstrated an improvement in glucose utilization. However, vanadyl sulfate was ineffective when administered to animals which lost their insulin secretion capacity on protracted HE diet, but substantially reduced the hyperglycemia when given together with exogenous insulin. The in vitro insulin activation of liver and muscle insulin receptors isolated from vanadyl treated Psammomys was ineffective. The in vivo vanadyl treatment restored muscle GLUT4 total protein and mRNA contents in addition to membrane GLUT4 protein, in accordance with the increased glucose utilization during the clamp study. These results indicate that short-term vanadyl sulfate treatment corrects the nutritionally induced, insulin resistant diabetes. This action requires the presence of insulin for its beneficial effect. Thus, vanadyl action in P. obesus appears to be the result of insulin potentiation rather than mimicking, with activation of the signaling pathway proteins leading to GLUT4 translocation, probably distal to the insulin receptor.

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Partial preservation of pancreatic β-cells by vanadian: Evidence for long-term amelioration of diabetes

Cited by 40 publications

References 42 publications

Distinct glucose lowering and beta cell protective effects of vanadium and food restriction in streptozotocin-diabetes

Distinct glucose lowering and beta cell protective effects of vanadium and food restriction in streptozotocin-diabetes

Effective control of glycemic status and toxicity in Zucker diabetic fatty rats with an orally administered vanadate compound

Treatment of diabetes with vanadium salts: general overview and amelioration of nutritionally induced diabetes in thePsammomys obesus gerbil

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