Plasma sialic acid in animal models of diabetes mellitus: evidence for modulation of sialic acid concentrations by insulin deficiency.
An elevated circulating sialic acid concentration is a risk factor for cardiovascular disease. Serum sialic acid levels are elevated in NIDDM but not in uncomplicated IDDM. To study why sialic acid is increased in some types of diabetes, we assayed plasma sialic acid in various animal models of diabetes: obese (ob/ob) mice, before and after streptozotocin treatment, neonatal streptozotocin-treated (nSTZ) rats, and diabetic BB rats during and after insulin treatment. In obese mice, which exhibit moderate hyperglycemia and marked hyperinsulinemia, plasma sialic acid was decreased by 45% (fed) and 42% (fasted), compared to lean controls. Fasting reduced plasma glucose and insulin but increased sialic acid in the obese and lean mice. There was a negative correlation (r = -0.84, P < 0.001) between log plasma insulin and sialic acid in the lean and obese mice. The plasma sialic acid:globulin ratio was reduced by 35% in obese mice vs. lean controls, indicating that there may be altered sialylation of glycoproteins in obese mice. Streptozotocin treatment of obese and lean mice reduced plasma insulin but increased sialic acid. In nSTZ rats, hyperglycemia was associated with mild hypoinsulinemia, but not significantly different from control animals, and sialic acid was not altered. In diabetic BB rats, plasma glucose rose from a mean of 4.9 to 23.5 mM 48 hr after insulin withdrawal but sialic acid did not change. We conclude that an elevated plasma sialic acid level is associated with marked insulin deficiency, rather than hyperglycemia per se. The magnitude and speed of this change in sialic acid varies between species.
Pickup
J C
JC
Division of Chemical Pathology, United Medical and Dental Schools, Guy's Hospital, London, UK.
Day
C
C
Bailey
C J
CJ
Samuel
A
A
Chusney
G D
GD
Garland
H O
HO
Hamilton
K
K
Balment
R J
RJ
D000818:Animals; D000831:Animals, Newborn; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D007328:Insulin / Q000172:deficiency*; D051379:Mice; D008815:Mice, Inbred Strains; D008820:Mice, Obese; D019158:N-Acetylneuraminic Acid; D051381:Rats; D011913:Rats, Inbred BB; D012712:Serum Globulins / Q000378:metabolism; D012794:Sialic Acids / Q000097:blood*; D013311:Streptozocin
D007328:Insulin; D012712:Serum Globulins; D012794:Sialic Acids; D013311:Streptozocin; D019158:N-Acetylneuraminic Acid