Beneficial effect of flax seeds in streptozotocin (STZ) induced diabetic mice: isolation of active fraction having islet regenerative and glucosidase inhibitory properties
Beneficial effect of flax seeds in streptozotocin (STZ) induced diabetic mice: isolation of active fraction having islet regenerative and glucosidase inhibitory properties
Year: 2013
Authors: Dusane, M.B. Joshi, B.N.
Publication Name: Can. J. Physiol. Pharmacol
Publication Details: Volume 91; Pages 325-331
Abstract:
Diabetes mellitus is a metabolic disorder that affects millions of people worldwide. Present study highlights the antidiabetogenic property of Linum usitassimum active fraction (LU6) in streptozotocin (STZ) induced diabetic Swiss mice. Treatment with LU6 fraction showed improved glucose utilization with increase in liver glucose6 phosphate dehydrogenase enzyme activity and normal glycogenesis in hepatic and muscle tissues. Reduction in pancreatic and intestinal glucosidase inhibitory activity was observed with LU6 treatment, indicating beneficial effects in reducing postprandial hyperglycemia (PPHG). Normalization of plasma insulin and Cpeptide levels were observed in diabetic mice, indicating endogenous insulin secretion after the treatment with LU6. The histochemical and immunohistochemical analysis on pancreatic islets suggests the role of LU6 fraction in islet regeneration and insulin secretion as evident in increase functional pancreatic islets producing insulin. Furthermore, significant insulin producing islet formation was also observed in in vitro PANC1 cells after LU6 treatment, indicating the
cellular aggregates to be newly formed islets. This suggests the potential of LU6 fraction in the formation of new islets in vitro, as well as in vivo. Thus, LU6 can be used as a neutraceutical based first line treatment for diabetes. (Authors abstract)
There are many reports of plants showing pancreatic islet regeneration and increase in insulin secretion in diabetic conditions in vitro, as well as in vivo. Flaxseed contains biologically active components such as linolenic acid and plant lignin secoisolariciresinol diglycoside (SDG).
In an earlier article, the authors demonstrated the in vitro murine pancreatic glucosidase inhibitory activity of L. usitassimum. The chloroform extract of L. usitassimum showed improved fasting blood glucose level and pancreatic islet regenerative property 1 in treated streptozotocin (STZ) induced diabetic mice. In the present study the chloroform extract of L. usitassimum was further fractionated to isolate the active component. The study reports that the active component of L. usitassimum is responsible for protecting pancreatic islets and enhancing insulin secretion.
The LU6 fraction was able to inhibit the pancreatic and intestinal glucosidase, suggesting LU6 possess beneficial effect in reducing postprandial hyperglycemia (PPHG) in diabetes. The normalization in G6PD activity, increase in hepatic and muscle glycogen contents, and utilization of glucose in OGTT indicates normal glucose metabolism after LU6 treatment. The increase in plasma insulin level along with the corresponding increase in C peptide level indicated endogenous secretion of insulin, which indicate that the islets are functional in LU6 treated mice .
As LU6 has shown both islet regeneration and glucosidase inhibitory activity, the authors hypothesized that LU6 may be acting on the glucagon-like peptide (GLP1), which is a hormone involved in islet regeneration and insulin secretary activity. It is known that glucosidase inhibition is considered to be an acceptable contributing factor for stimulating GLP1 secretion , which binds to specific G-protein-coupled receptors on pancreatic cells to stimulate insulin secretion via cAMP dependent pathways. In conclusion, the present investigation is important in that it is the first biochemical study on the effect of the active fraction LU6 isolated from the chloroform extract of L. usitassimum with respect to islet regeneration and insulin secretory activity. The reducing effects of L. usitassimum on postprandial glucose may be able to decrease the risk of developing type II diabetes in patients with impaired glucose tolerance. (Editors comments)