Among the Cree of northern Quebec, the disproportionately high rate of diabetic complications is largely due to the cultural inadequacy of modern therapies for type 2 diabetes. To establish culturally adapted antidiabetic treatments, our team identified several candidate plant species used by the Cree to treat symptoms of diabetes. An initial study focused on 8 species and revealed that most possess significant in vitro antidiabetic activity. The purpose of the present study was to assess a further 9 species identified through the ethnobotanical survey. Crude plant extracts were screened for (i) potentiation of basal and insulin-stimulated glucose uptake by skeletal muscle cells (C2C12) and adipocytes (3T3-L1); (ii) potentiation of glucose-stimulated insulin secretion by pancreatic beta cells (betaTC); (iii) potentiation of adipogenesis in 3T3-L1 cells; (iv) protection against glucose toxicity and glucose deprivation in PC12-AC neuronal precursor cells; and (v) diphenylpicrylhydrazyl (DPPH) oxygen free radical scavenging. Four species potentiated basal glucose uptake in muscle cells or adipocytes, one species being as potent as metformin. Adipogenesis was accelerated by 4 species with a potency roughly half that of rosiglitazone. Five species protected PC12-AC cells against glucose toxicity and 4 protected against glucose deprivation. Five species exhibited antioxidant activity comparable to ascorbic acid. However, no species increased insulin secretion. The present study revealed that Gaultheria hispidula, Rhododendron tomentosum, and Vaccinium vitis-idaea exhibit a promising profile of antidiabetic potential and are good candidates for more in-depth evaluation.

The incidence of type 2 diabetes mellitus has reached epidemic proportions worldwide. Canadian aboriginal communities, particularly the Cree Nation of Eeyou Istchee, have been identified as a high-risk population. Culturally acceptable treatment options are limited notably for diabetic complications resulting in peripheral neuropathy. Here, we describe results of an ongoing collaborative research project with Cree of Eeyou Istchee to identify botanicals capable of protecting peripheral neuronal precursors from glucose toxicity and glucose deprivation in vitro. Polar fractions of three plant organs (needles, cone, and bark) collected from Picea glauca (Moench) Voss (Pinaceae), were tested for toxicity under normoglucose, glucotoxicity, and glucose deprivation conditions. The profile of phenolic metabolites in each extract was first characterized by high-performance liquid chromatography-diode array detection-atmospheric pressure chemical ionisation mass spectrometry (HPLC-DAD-APCI/MS). We report here that these fractions are well-tolerated by PC12 neuronal precursors under normoglucose conditions. LD 50 concentrations of needle extracts exceeded 100 µg/mL, whereas the LD 50 of bark and cone extracts was 40 and 36.4 µg/mL, respectively. We further show that the cytoprotective properties of minhikw after glucose challenge are concentration-dependent and organ-specific. Needle * Dedicated to John Thor Arnason of the University of Ottawa, Department of Biology, on the occasion of his sixtieth birthday. extracts protected PC12 cells from both glucotoxicity and glucose deprivation. Bark extracts had negligible activity. Cone extracts further impaired PC12 cell glucose tolerance. This study provides the first validation of antidiabetic activity of minhikw organs at the cellular level relevant to the management of diabetic peripheral neuropathy.