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. 2018 Jul 18:9:739.
doi: 10.3389/fphar.2018.00739. eCollection 2018.

Formononetin Treatment in Type 2 Diabetic Rats Reduces Insulin Resistance and Hyperglycemia

Manisha J Oza  1   2 , Yogesh A Kulkarni  1
Affiliations

Formononetin Treatment in Type 2 Diabetic Rats Reduces Insulin Resistance and Hyperglycemia

Manisha J Oza et al. Front Pharmacol. .

Abstract

Type 2 diabetic mellitus is a multifactorial metabolic disorder affecting huge population around the world. This indicates that there is an urgent unmet need of cost effective, new treatment strategies for type 2 diabetes mellitus with no or less side effects. Phenolic compounds including isoflavones are known for their beneficial effect in metabolic disorders. The present work was intended to find out efficacy of formononetin, an isoflavone treatment in experimental model of type 2 diabetes. Type 2 diabetes mellitus was induced by feeding high fat diet for 2 weeks prior to streptozotocin administration in Sprague Dawley rats. Diabetic animals were treated with formononetin for 28 days at three dose level, i.e., 10, 20, and 40 mg/kg body weight orally. The effect of formononetin treatment on various parameters such as plasma glucose, glucose tolerance, insulin, HOMA-IR, lipid profile, hepatic glycogen content, glycohaemoglobin and SIRT1 expression in pancreatic tissue was measured. Histopathological changes in pancreatic tissue were also studied. Results of the study demonstrate that formononetin treatment reduces blood glucose level significantly (p < 0.001) at all the three dose level. It also improved glucose tolerance, insulin sensitivity and lipid profile along with reduction in glycohaemoglobin content in blood. Formononetin treatment also improved hepatic glycogen level profoundly in diabetic rats. Determination of SIRT1 expression in pancreatic tissue by immunohistochemical analysis showed that formononetin treatment increases the expression of SIRT1 in pancreatic tissue. Histopathological study showed that treatment with formononetin protects pancreatic beta cells from necro-degeneration and atrophic effect. It can be concluded that formononetin treatment reduces insulin resistance and attenuate hyperglycemia in type 2 diabetes which may be due to increasing expression of SIRT1 in pancreatic tissues.

Keywords: SIRT1; formononetin; high fat diet; isoflavone; streptozotocin; type 2 diabetes mellitus.

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Figures

FIGURE 1
FIGURE 1
Effect of formononetin treatment on body weight in type 2 diabetic rats. Values are expressed as Mean ± SEM (n = 6).
FIGURE 2
FIGURE 2
Effect of formononetin treatment in blood glucose level. Values are expressed as Mean ± S.E.M. ∗p < 0.05, ∗∗∗p < 0.001 when compared with diabetic control. ###p < 0.001 when compared to normal control (n = 6).
FIGURE 3
FIGURE 3
Effect of formononetin treatment on oral glucose tolerance in type 2 diabetic rats. Values are expressed as Mean ± SEM. ∗p < 0.05, ∗∗p < 0.01, and ∗∗∗p < 0.001 when compared with diabetic control. ###p < 0.001 when compared to normal control (n = 6).
FIGURE 4
FIGURE 4
Light microscopic pictures of immunohistochemical staining. (A) Normal Control, (B) Diabetes Control, (C) Diabetic + Formononetin (10 mg/kg, orally), (D). Diabetic + Formononetin (20 mg/kg, orally), (E) Diabetic + Formononetin (40 mg/kg, orally), (F) Diabetic + glipizide (5 mg/kg, orally). Large arrow Shows expression of SIRT1 in Islet of Langerhans and small arrow shows expression of SIRT1 in acini of exocrine pancreas (SIRT1 immunostaining, 400X).
FIGURE 5
FIGURE 5
Treatment with Formononetin increases the optical density of SIRT1 in immunohistochemical staining in pancreatic tissues. All values are expressed as Mean ± SEM (n = 6), #p < 0.05, when compared with normal control group, ∗p < 0.05, when compared with diabetic control group.
FIGURE 6
FIGURE 6
Light microscopic pictures of HE stain of pancreatic tissue. (A) Normal Control: Pancreas: Showing normal histology, acinus (arrow head), interlobular duct (large arrow), intercalated duct (small arrow), Islet of Langerhans (star) {H & E, 400×}. (B) Diabetes Control: Pancreas: Showing hyperplastic acini of exocrine pancreas (arrow head), atrophy and degeneration of Islet of Langerhans (small arrow) {H & E, 400×}. (C) Diabetic + Formononetin (10 mg/kg, orally): Pancreas: Showing degeneration of Islet of Langerhans (small arrow) {H & E, 400×}. (D) Diabetic + Formononetin (10 mg/kg, orally): Pancreas: Showing adipose tissue deposition at acini (small arrow) {H & E, 400×}. (E) Diabetic + Formononetin (40 mg/kg, orally): Pancreas: Showing lymphocytic infiltration (arrow) {H & E, 400×}. (F) Diabetic + glipizide (5 mg/kg, orally): Showing normal histology, acinus (arrow head), intercalated duct (small arrow), Islet of Langerhans (star) {H & E, 400×}.
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