Date Published: April 13, 2016
Publisher: Public Library of Science
Author(s): Alfred N. Murunga, David O. Miruka, Christine Driver, Fezile S. Nkomo, Snazo Z. Z. Cobongela, Peter M. O. Owira, Bridget Wagner.
Hypoglycemic effects of grapefruit juice are well known but the effects of naringin, its main flavonoid on glucose intolerance and metabolic complications in type 1 diabetes are not known.
To investigate the effects of naringin on glucose intolerance, oxidative stress and ketonemia in type 1 diabetic rats.
Sprague-Dawley rats divided into 5 groups (n = 7) were orally treated daily with 3.0 ml/kg body weight (BW)/day of distilled water (group 1) or 50 mg/kg BW of naringin (groups 2 and 4, respectively). Groups 3, 4 and 5 were given a single intra-peritoneal injection of 60 mg/kg BW of streptozotocin to induce diabetes. Group 3 was further treated with subcutaneous insulin (4.0 IU/kg BW) twice daily, respectively.
Stretozotocin (STZ) only-treated groups exhibited hyperglycemia, polydipsia, polyuria, weight loss, glucose intolerance, low fasting plasma insulin and reduced hepatic glycogen content compared to the control group. Furthermore they had significantly elevated Malondialdehyde (MDA), acetoacetate, β-hydroxybutyrate, anion gap and significantly reduced blood pH and plasma bicarbonate compared to the control group. Naringin treatment significantly improved Fasting Plasma Insulin (FPI), hepatic glycogen content, malondialdehyde, β-hydroxybutyrate, acetoacetate, bicarbonate, blood pH and anion gap but not Fasting Blood Glucose (FBG) compared to the STZ only-treated group.
Naringin is not hypoglycemic but ameliorates ketoacidosis and oxidative stress. Naringin supplements could therefore mitigate complications of diabetic ketoacidosis.
Diabetes mellitus (DM) is a consequence or absolute of relative insulin deficiency leading to hyperglycemia and concomitant disturbances in carbohydrate, fat and protein metabolism [1, 2].
This study was based on a typical type 1 diabetes model created with STZ which selectively and irreversibly completely destroys the pancreatic β-cells by oxidative damage. Interestingly, naringin treatment of normal rats was associated with relative increase in FPI concentrations (Fig 6). Considering that insulin treatment similarly increased FPI in diabetic animals, we speculate that the antioxidant effects of naringin reduced oxidative stress in the pancreatic β-cell mitochondria leading to increased ATP synthesis and subsequent insulin secretion. By its anabolic effects, insulin similarly to naringin, boosted residual anti-oxidant capacity of the β-cells leading to increased insulin secretion. This could have limited oxidative damage of STZ to allow the β-cells to retain some residual activity. Potential insulinotropic effects of naringin have only recently been demonstrated .
Although naringin did not improve glucose intolerance, it was associated with reversal of weight loss, improved glycogen storage and insulin secretion in diabetic rats. However, naringin abrogated metabolic acidosis suggesting a role in the management of DKA. These actions of naringin appear to be mediated in part by its powerful antioxidant affects. Our findings therefore suggest that naringin as a nutritional supplement could be protective against ketonemia in type 1 diabetes patients and may be used as adjunct therapy pending further clinical studies.