The effects of some aldose sugars on the oxygen uptake in stimulated and non-stimulated isolated mouse pancreatic islets: configurational and conformational factors
Hellerstrom, C.; Marsden, N.V.
Physiological Chemistry and Physics 14(6): 495-502
1982
ISSN/ISBN: 0031-9325 PMID: 6764817 Document Number: 193099
The rate of O2 uptake in pancreatic islets from obese hyperglycemic mice was measured by a Cartesian diver method in the presence of several hexoses and pentoses. The rate of O2 uptake was increased only by D-glucose and, to a lesser extent by D-mannose indicating that the only deviation from the D-glucose structure (L-glucose was without effect) allowing retention of the stimulatory effect is an altered orientation of the hydroxyl at C-2. Removal of this hydroxyl (2-deoxy-D-glucose) abolished the stimulatory effect. None of the sugars tested reduced the endogenous rate of O2 uptake. When the rate of O2 uptake was stimulated by D-glucose or D-mannose, this stimulatory effect was reduced by certain other sugars. The inhibitory effect was always exerted on both D-glucose and D-mannose-stimulated islets and the reduction was always relatively greater in the case of the weaker stimulant, D-mannose. The 6-deoxy derivatives of D-mannose and D-glucose had inhibitory effects on the uptake of O2 stimulated by either D-mannose or D-glucose; 6-deoxy-D-glucose had the greater effect, being the most potent in this respect of all the sugars tested. Other sugars which inhibited glucose or mannose-stimulated O2 uptake were D-xylose, D-altrose and D-talose. D-Glucose and D-mannose apparently have a common metabolic interaction locus in the islet .beta.-cell. Homomorphs of D-glucose with either the hydroxymethyl group at C-5 deoxygenated or entirely absent can probably interfere with the glucose interaction although they themselves are unable to stimulate O2 uptake. In the case of D-mannose, only the 6-deoxy homomorph was manifestly inhibitory but it is anticipated that the homomorphous pentose, D-lyxose although potentially inhibitory should only have a small effect and this might account for the present failure to observe an effect. The inhibitory effects of D-talose and D-altrose apparently cannot be interpreted on configuration grounds alone and it is suggested that their inhibitory activity may be correlated with their marked conformational instability which may thus permit them to interact with the metabolic processes of the .beta.-cell.