The
glucose-lowering effects of lupin seeds involve the combined action of several components. The present study investigates the influence of one of the main
quinolizidine alkaloids,
lupanine, on pancreatic beta cells and in an animal model of type-2
diabetes mellitus. In vitro studies were performed with
insulin-secreting INS-1E cells or islets of C57BL/6 mice. In the in vivo experiments,
hyperglycemia was induced in rats by injecting
streptozotocin (65 mg/kg
body weight). In the presence of 15 mmol/
L glucose, insulin secretion was significantly elevated by 0.5 mmol/L
lupanine, whereas the
alkaloid did not stimulate
insulin release with lower
glucose concentrations. In islets treated with
l-arginine, the potentiating effect of
lupanine already occurred at 8 mmol/
L glucose.
Lupanine increased the expression of the Ins-1 gene. The potentiating effect on secretion was correlated to membrane depolarization and an increase in the frequency of Ca(2+) action potentials. Determination of the current through
ATP-dependent K⁺
channels (KATP channels) revealed that
lupanine directly inhibited the channel. The effect was dose-dependent but, even with a high
lupanine concentration of 1 mmol/L or after a prolonged exposure time (12 h), the
KATP channel block was incomplete.
Oral administration of
lupanine did not induce
hypoglycemia. By contrast,
lupanine improved
glycemic control in response to an oral
glucose tolerance test in
streptozotocin-diabetic rats. In summary,
lupanine acts as a positive modulator of
insulin release obviously without a risk for
hypoglycemic episodes.