Effect of in vitro glucose and diabetic hyperglycemia on mouse kidney protein synthesis: relevance to diabetic microangiopathy.
To test the possible roles of diabetic hyperglycemia, we studied the in vitro effect of increasing glucose concentrations (5.0-27.5 mmol/L) on protein synthesis (PS) of the kidneys from "adult" male albino Swiss mice. In mouse kidney cortex slices, PS (3H-leucine incorporation into trichloroacetic acid-precipitable material), measured as cpm/mg protein/45 minutes, was already stimulated by 5.0 mmol/L of glucose (+24%, P < .05). At supraphysiologic glucose concentrations, PS was stimulated by 48% at 8.8 mmol/L of glucose and 31% at 13.6 mmol/L of glucose (P < .05, compared with the value observed at 5.0 mmol/L of glucose). However, the highest glucose levels (15.4 mmol/L and 27.5 mmol/L) were no longer effective. Other substrates (1.25 mmol/L or 6.26 mmol/L palmitic acid and 100 mcmol/L sorbitol) were without effect. Similar results were obtained when data were expressed as cpm/mg DNA/45 minutes. In contrast to adult mice, "young" mice showed the maximum stimulatory effect (+86%, P < .02), with a glucose concentration still in the nondiabetic range (6.6 mmol/L). However, in the "older" mice maximum stimulation was observed in the presence of high glucose concentrations (15.4 mmol/L and 27.5 mmol/L) with 52% (P < .02) and 26% (P < .05) increases, respectively, vs the value recorded at 5 mmol/L of glucose. With regard to the in vivo effect of diabetic hyperglycemia, the renal PS of 3-day streptozotocin diabetic mice was moderately increased, whereas the liver PS was markedly reduced. The effects of in vitro glucose and in vivo diabetic hyperglycemia, as modulated by both the concentration of glucose and the age, may lead to diabetic renal hypertrophy and the increased formation/accumulation of glycoproteins, thus contributing to microangiopathy.
Iannello
Silvia
S
Department of Internal Medicine, University of Catania, Garibaldi Hospital, P.zza S. Maria di Gesù, Catania, Italy.
Milazzo
Paolina
P
Bordonaro
Fabio
F
Belfiore
Francesco
F
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003925:Diabetic Angiopathies / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology*; D006943:Hyperglycemia / Q000378:metabolism*; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051379:Mice; D014176:Protein Biosynthesis / Q000187:drug effects*
D005947:Glucose