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Insulinotropic effects of vanadate
Abstract:
Vanadium compounds are known to affect multiple membrane and cytosolic phosphoenzymes from various tissues; the most characterized effect is the inhibition of Na+-K+-ATPase. Since we previously reported that immunoreactive insulin (IRI) secretagogues tend to inhibit rat islet cation-dependent ATPases, we examined the effects of sodium vanadate on rat IRI secretion from incubated and perifused rat islets. In the presence of 2.4 mM Ca2+, vanadate (10(-3) M) induced biphasic IRI secretion with a background glucose of 100 mg/dl. In the absence of extracellular Ca2+, IRI released from incubated islets by vanadate at 100 and 300 mg/dl glucose was doubled and tripled, respectively. Furthermore, this stimulatory effect was completely abolished by known inhibitors of IRI release such as somatostatin, epinephrine, and diphenylhydantoin. Although we found the expected dose-dependent inhibition by vanadate of islet membrane Na+-K+-ATPase activity, the mechanism of action of vanadate on IRI secretion remains unknown. Vanadate probably interacts in a complex fashion with different islet phosphoenzymes and may prove to be a useful probe to further unravel the mechanisms leading to insulin secretion.
Insights
Sodium vanadate stimulates insulin secretion from rat islets in a biphasic manner, particularly when extracellular calcium is absent. Its precise mechanism on insulin release remains under investigation.
Area of Science:
- Biochemistry
- Endocrinology
- Cell Physiology
Background:
- Vanadium compounds, notably sodium vanadate, are known inhibitors of Na+-K+-ATPase and other phosphoenzymes.
- Previous research indicated that insulin secretagogues can inhibit rat islet cation-dependent ATPases.
Purpose of the Study:
- To investigate the effects of sodium vanadate on rat insulin secretion from pancreatic islets.
- To explore the relationship between vanadate, calcium, glucose, and insulin release.
Main Methods:
- Incubation and perifusion of rat islets.
- Measurement of immunoreactive insulin (IRI) secretion.
- Assay of islet membrane Na+-K+-ATPase activity.
- Use of calcium, glucose, somatostatin, epinephrine, and diphenylhydantoin as experimental modulators.
Main Results:
- Sodium vanadate induced biphasic IRI secretion in the presence of 2.4 mM Ca2+ and 100 mg/dl glucose.
- In the absence of extracellular Ca2+, vanadate significantly increased IRI release at both 100 and 300 mg/dl glucose.
- The stimulatory effect of vanadate on IRI secretion was abolished by somatostatin, epinephrine, and diphenylhydantoin.
- Vanadate demonstrated a dose-dependent inhibition of islet membrane Na+-K+-ATPase activity.
Conclusions:
- Sodium vanadate stimulates insulin secretion from rat islets, with a pronounced effect in low extracellular calcium conditions.
- While vanadate inhibits islet Na+-K+-ATPase, its exact mechanism for stimulating insulin secretion is complex and likely involves multiple islet phosphoenzymes.
- Vanadate may serve as a valuable tool for elucidating the intricate mechanisms of insulin secretion.