JOURNAL OF MEDICINAL FOOD J Med Food 10 (1) 2007, 41–48 © Mary Ann Liebert, Inc. and Korean Society of Food Science and Nutrition DOI: 10.1089/jmf.2005.034 Gluconeogenic Substrates and Hepatic Gluconeogenic Enzymes in Streptozotocin-Diabetic Rats: Effect of Mulberry (Morus indica L.) Leaves B. Andallu 1 and N.C.Varadacharyulu 2 1 Department of Home Science, Sri Sathya Sai Institute of Higher Learning; and 2 Department of Biochemistry, Sri Krishnadevaraya University, Anantapur, Andhra Pradesh, India ABSTRACT Mulberry (Morus indica L.) leaves, the sole food of the silk worm, were evaluated for antidiabetic effects in streptozotocin (STZ)-diabetic rats. Treatment with dried mulberry leaf powder at 25% of the diet for a period of 8 weeks was found to be remarkably beneficial to STZ-diabetic rats as evidenced by controlled hyperglycemia and glycosuria. In addition, mulberry leaves countered (reversed) the alterations in gluconeogenic substrates in STZ-diabetic rats as indicated by signifi- cant reduction in serum pyruvic and lactic acid levels, a significant increase in proteins and a significant decrease in free amino acid, urea, and creatinine levels in blood, and a decreased urinary excretion of urea and creatinine. Anomalies in the activities of hepatic gluconeogenic enzymes associated with impaired glucose homeostasis in STZ-diabetic rats were amelio- rated by feeding the mulberry leaf-supplemented diet, indicating that control over hyperglycemia and associated complica- tions in the diabetic state by mulberry leaves is by way of regulation of gluconeogenesis. With respect to all the parameters, mulberry leaves were more effective than the oral hypoglycemic drug glibenclamide. KEY WORDS: • blood glucose • creatinine • lactic acid • mulberry leaves • pyruvic acid • streptozotocin-diabetic rats • urea 41 INTRODUCTION T HE TERM DIABETES MELLITUS describes a metabolic dis- order of multiple etiology characterized by chronic hy- perglycemia with disturbances of carbohydrate, fat, and pro- tein metabolisms. The metabolic disorders are due to the impaired action of insulin in target tissues resulting from in- sensitivity or lack of insulin. 1 The incidence of diabetes mel- litus has increased alarmingly during the past few decades, posing a major health hazard at the dusk of 20 th century and a major health threat at the dawn of the 21 st century. 2 A sci- entific investigation of traditional herbal remedies for dia- betes provides valuable leads for the development of alter- native drugs and therapeutic strategies. Alternatives are clearly needed because of the inability of current therapies to control all of the pathological aspects of diabetes and the high cost for many rural populations, particularly in devel- oping countries. 3 In the last few decades, there has been an exponential growth in the field of herbal medicines. It is gaining acceptance in developed and developing countries owing to its natural origin and lesser side effects. 4 Plant foods play an important role in the management of diabetes mellitus, and some vegetables are potential hypoglycemic agents. 5 Mulberry leaves are used in traditional Chinese medicine for their antihyperglycemic actions. Fagomine, one of the six N-containing sugars isolated from mulberry leaves, was reported to potentiate glucose-induced insulin release similar to that of glibenclamide. 6 Many earlier in- vestigators 6–8 used glibenclamide in diabetic animal studies to compare the efficiency of various phytochemicals/thera- peutic extracts/diets and other pharmacological antidiabetic compounds. Little is known about the effects of long-term consump- tion of mulberry leaves on gluconeogenic substrates and on the activity of gluconeogenic enzymes in diabetes mellitus. Therefore, this study investigated the effects of mulberry leaves on various biochemical parameters, on metabolites of carbohydrates and proteins, and on the activity of hepatic gluconeogenic enzymes. MATERIALS AND METHODS Animals Thirty male Wistar albino rats (weighing 150–200 g) were obtained from the National Centre for Laboratory Animal Sciences, National Institute of Nutrition, Hyderabad, India and divided into five groups of six each: group 1, normal control; group 2, normal rats maintained on mulberry leaf powder diet; group 3, diabetic control; group 4, diabetic rats Manuscript received 26 May 2005. Revision accepted 26 July 2006. Address reprint requests to: B. Andallu, Department of Home Science, Sri Sathya Sai In- stitute of Higher Learning, Anantapur-515001, Andhra Pradesh, India, E-mail: andal- lusss@rediffmail.com