INSULIN-RESISTANCE IN SPONTANEOUSLY HYPERTENSIVE RATS - DIFFERENCE ININTERPRETATION BASED ON INSULIN INFUSION RATE OR ON PLASMA-INSULIN INGLUCOSE CLAMP STUDIES
Rh. Rao, INSULIN-RESISTANCE IN SPONTANEOUSLY HYPERTENSIVE RATS - DIFFERENCE ININTERPRETATION BASED ON INSULIN INFUSION RATE OR ON PLASMA-INSULIN INGLUCOSE CLAMP STUDIES, Diabetes, 42(9), 1993, pp. 1364-1371
Citations number
41
Categorie Soggetti
Endocrynology & Metabolism","Medicine, General & Internal
Isotopic glucose turnover was measured during euglycemic glucose clamp
studies in spontaneously hypertensive rats and normotensive Wistar-Ky
oto control rats, under pentobarbital sodium anesthesia. At an insulin
infusion rate of 4 mU . kg-1 . min-1, glucose disposal rate and hepat
ic glucose output were not significantly different in either group, at
a plasma glucose of 6 mM. However, steady-state plasma insulin levels
in spontaneously hypertensive rats were more than double those in Wis
tar-Kyoto rats (2.34 +/- 0.16 [means +/- SE] vs. 6.78 +/- 0.58 nM, P <
0.00005, n = 7 in each group). Additional studies (n = 30 in spontane
ously hypertensive rats and n = 32 in Wistar-Kyoto control rats) were
conducted to match insulin levels in the two groups over a wide range,
using infusion rates of 0.5-10 mU . kg-1 . min-1. When the responses
of glucose disposal rate and hepatic glucose output to insulin were an
alyzed from the standpoint of plasma insulin levels, a highly signific
ant difference was seen in the response to insulin between spontaneous
ly hypertensive rats and Wistar-Kyoto rats, for both glucose disposal
rate (P < 0.000005) and hepatic glucose output (P = 0.00007). The slop
e of the regression line for glucose disposal rate versus plasma insul
in was lower in spontaneously hypertensive rats compared with Wistar-K
yoto rats (2.652 vs. 4.864, P < 0.001), indicating that insulin stimul
ation of glucose disposal rate was reduced by 50% in spontaneously hyp
ertensive rats. The slope of hepatic glucose output versus plasma insu
lin was 0.739 in spontaneously hypertensive rats, indicating impaired
suppression of hepatic glucose output, compared with Wistar-Kyoto rats
, where the slope was -10.3, (P < 0.001 vs. spontaneously hypertensive
rats). The clearance of insulin showed great variability in both grou
ps but was much lower in spontaneously hypertensive rats compared with
Wistar-Kyoto rats (6.7 +/- 0.9 vs. 14.9 +/- 1.3 ml . kg-1 . min-1, P
< 0.000005). Post hoc power analysis showed that the within-group vari
ation resulted in low power and high risk of type II errors when compa
risons were restricted to a small sample size (n = 8). We conclude tha
t insulin sensitivity is impaired in spontaneously hypertensive rats w
hen expressed as a function of the ambient plasma insulin level, but n
ot when expressed as a function of the administered dose of insulin, b
ecause of the risk of type II errors caused by the great variability i
n insulin concentrations at any given insulin infusion rate when the s
ample size is small.