Infusion of pH 2.0 D-chiro-inositol glycan insulin putative mediator normalizes plasma glucose in streptozotocin diabetic rats at a dose equivalent to insulin without inducing hypoglycaemia.
We compared the effects of infusing a chemically defined chiro-inositol glycan putative insulin mediator with an equivalent dose of insulin in low-dose (45 mg/kg) streptozotocin diabetic rats. Insulin decreased plasma glucose levels from 17.32 +/- 0.17 to 3.96 +/- 0.064 mmol/l (p < 0.0002) in 120 min, a decrease of 77.13%, while the putative mediator promoted a decrease in plasma glucose from 14.85 +/- 0.084 to 7.22 +/- 0.13 mmol/l (p < 0.007) in 60 min. The putative mediator maintained euglycaemia over the ensuing 60 min with a plasma glucose level of 7.01 +/- 0.10 mmol/l at 120 min. Thus, insulin further reduced the plasma glucose from euglycaemia at 60 min to produce hypoglycaemia at 120 min. The lack of production of hypoglycaemia by the putative mediator can be explained by its inhibition of glucose-stimulated insulin secretion by the islet beta cells, thus providing a potential negative feedback regulatory mechanism; or by its selective action on muscle to increase glycogen synthesis. The significance of these results in terms of future directions in drug design is herein considered.
Fonteles
M C
MC
Clinical Research Unit, Federal University of Ceara/UECe, Fortaleza, Ceara, Brazil.
Huang
L C
LC
Larner
J
J
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007003:Hypoglycemia / Q000378:metabolism / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007295:Inositol Phosphates / Q000494:pharmacology* / Q000627:therapeutic use; D007328:Insulin / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D011134:Polysaccharides / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007295:Inositol Phosphates; D007328:Insulin; D011134:Polysaccharides; C028039:inositol phosphate glycan