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Nigella sativa L. 'Black cumin' (Ranunculaceae) is one of the plants commonly used in Moroccan folk medicine for treatment of various ailments including diabetes mellitus. The present study was undertaken to investigate the effect of different N. sativa seed extracts on insulin secretion. Different fractions of the seed were prepared: the defatted fraction (HR II), which was divided into two subfractions: the first (HR III) containing acidic and neutral compounds and the second (HR IV) containing basic compounds. The insulin secretory effects of these extracts were evaluated individually at different concentrations (0.01, 0.1, 1 and 5 mg/mL), in vitro in isolated rat pancreatic islets in the presence of 8.3 mmol/L glucose. The results show that addition of the defatted whole extract or of the basic subfraction of the seed in the incubation medium significantly increased glucose-induced insulin release from the islets. In the case of the acidic and neutral subfraction, the stimulatory effect was observed only for the higher concentration (5 mg/mL). However, a clear concentration-dependent increase in insulin release from isolated pancreatic islets was observed for the basic subfraction. Our data show that the antidiabetic properties of N. sativa seeds may be, at least partly, mediated by stimulated insulin release, and that the basic subfraction largely contributes to this stimulatory effect. Further phytochemical studies are underway in order to isolate the pharmacological compound(s) responsible for the insulinotropic effect of N. sativa seeds.

We have recently shown in vitro that 4-hydroxyisoleucine (4-OH-Ile), an amino acid extracted from fenugreek seeds, potentiates insulin secretion in a glucose-dependent manner. The present study was designed to investigate whether 4-OH-Ile could exert in vivo insulinotropic and antidiabetic properties. For this purpose, intravenous or oral glucose tolerance tests (IVGTTs and OGTTs, respectively) were performed not only in normal animals but also in a type II diabetes rat model. During IVGTT in normal rats or OGTT in normal dogs, 4-OH-Ile (18 mg/kg) improved glucose tolerance. The lactonic form of 4-OH-Ile was ineffective in normal rats. In non-insulin-dependent diabetic (NIDD) rats, a single intravenous administration of 4-OH-Ile (50 mg/kg) partially restored glucose-induced insulin response without affecting glucose tolerance; a 6-day subchronic administration of 4-OH-Ile (50 mg/kg, daily) reduced basal hyperglycemia, decreased basal insulinemia, and slightly, but significantly, improved glucose tolerance. In vitro, 4-OH-Ile (200 microM) potentiated glucose (16.7 mM)-induced insulin release from NIDD rat-isolated islets. So, the antidiabetic effects of 4-OH-Ile on NIDD rats result, at least in part, from a direct pancreatic B cell stimulation.

We report the characterization of a new insulinotropic compound, 4-hydroxyisoleucine. This amino acid has been extracted and purified from fenugreek seeds, which are known in traditional medicine for their antidiabetic properties. 4-Hydroxyisoleucine increases glucose-induced insulin release, in the concentration range of 100 micromol/l to 1 mmol/l, through a direct effect on isolated islets of Langerhans from both rats and humans. The stimulating effect of 4-hydroxyisoleucine was strictly glucose dependent; indeed, ineffective at low (3 mmol/l) or basal (5 mmol/l) glucose concentrations, the amino acid potentiated the insulin secretion induced by supranormal (6.6-16.7 mmol/l) concentrations of glucose. In addition, in the isolated perfused rat pancreas, we could show 1) that the pattern of insulin secretion induced by 4-hydroxyisoleucine was biphasic, 2) that this effect occurred in the absence of any change in pancreatic alpha- and delta-cell activity, and 3) that the more glucose concentration was increased, the more insulin response was amplified. Moreover, 4-hydroxyisoleucine did not interact with other agonists of insulin secretion (leucine, arginine, tolbutamide, glyceraldehyde). Therefore, we conclude that 4-hydroxyisoleucine insulinotropic activity might, at least in part, account for fenugreek seeds' antidiabetic properties. This secretagogue may be considered as a novel drug with potential interest for the treatment of NIDDM.

Fractions of fenugreek seed were added to the diet of normal or diabetic hypercholesterolaemic dogs for 8 days. The effects on levels of blood glucose, plasma glucagon and plasma cholesterol were investigated. The lipid extract had no effect. The defatted fraction which is rich in fibres (53.9%) and contains 4.8% of steroid saponins significantly lowered basal blood glucose (P less than 0.02), plasma glucagon (P less than 0.01) and plasma cholesterol (P less than 0.02) levels in normal dogs. The addition of this fraction to the food of diabetic hypercholesterolaemic dogs caused a decrease of cholesterolaemia (P less than 0.02) and reduced hyperglycaemia. In conclusion, the defatted portion of fenugreek seed induces a hypocholesterolaemic effect.

We have previously shown that the antidiabetic property of fenugreek seeds (Trigonella foenum graecum L.) is associated with the defatted seed material which is rich in fibers, saponins, and proteins. In the present work this defatted preparation was divided into two subfractions: subfraction "a" which contains the testa and endosperm and is rich in fibers (79.6%); and subfraction "b" which contains the cotyledons and axes and is rich in saponins (7.2%) and proteins (52.8%). We investigated the effects of each subfraction on hyperglycemia and the levels of pancreatic hormones when chronically administered to alloxan-diabetic dogs. Each subfraction was studied separately and was given to the dogs per os (mixed with the two daily meals), in addition to the insulin treatment (which was kept the same throughout the experiment) for a period of 21 days. The addition of subfraction "a" to insulin treatment resulted in a clear decrease of hyperglycemia and glycosuria accompanied by a reduction of the high plasma glucagon and somatostatin levels in diabetic dogs. The treatment also decreased the hyperglycemic response to the oral glucose tolerance test. In contrast the chronic administration of subfraction "b" had no effect on hyperglycemia or on the levels of pancreatic hormones in diabetic dogs. Our results show that the antidiabetic properties of fenugreek seeds are contained in the testa and endosperm. Although this subfraction is rich in fibers (high viscosity; 115 cP), it is not possible to exclude the existence of one or more unknown active pharmacological compounds in this subfraction of the seed.