Studies of insulin resistance in the streptozotocin diabetic and BB rat: activation of low Km cAMP phosphodiesterase by insulin.
The streptozotocin diabetic rat (STZ-DM) has been the best animal model for the study of insulin-deficient diabetes. A spontaneous diabetic BB Wistar Rat (SDR) has now been evaluated as a model for insulin-dependent diabetes that more closely reflects this disease in humans. The authors assessed the ability of insulin to stimulate the Vmax of a low Km cAMP phosphodiesterase (PDE) in adipose tissue of control, streptozotocin diabetic (STZ-DM) rats, and spontaneous diabetic BB rats (SDR). In addition, the authors examined the effect of streptozotocin on the nondiabetic littermates of the SDR animal, the NDR rat. Insulin stimulated Vmax of low Km cAMP PDE in control rat adipose tissue by 20% at 5 minutes. Insulin also stimulated Vmax of both SDR and NDR by 50% at 5 minutes. In contrast to control and both subgroups of the BB rat (SDR and NDR), insulin stimulated adipose tissue from STZ-DM less than 10% at 5 minutes. NDR animals rendered diabetic with streptozotocin were more responsive to insulin. The data demonstrate some similarities and differences between streptozotocin-induced diabetes and spontaneous diabetes in the BB rat. Reduced responsiveness to insulin appears to be more a part characteristic of streptozotocin diabetes than diabetes in the BB rat. The absence of significant insulin resistance in the spontaneous diabetic BB rat also is more consistent with the pathophysiological mechanisms usually seen both in other insulin-dependent diabetic rat models and insulin-dependent diabetes in man. However, both animal models of diabetes, ie, STZ-DM and BB, like man, respond to insulin therapy.
Solomon
S S
SS
Research Services, Veterans Administration Medical Center, Memphis, TN 38104.
Deaton
J
J
Harris
G
G
Smoake
J A
JA
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism*; D000273:Adipose Tissue / Q000201:enzymology; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology*; D004789:Enzyme Activation; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D008297:Male; D051381:Rats; D011913:Rats, Inbred BB; D011919:Rats, Inbred Strains
D007328:Insulin; D015105:3',5'-Cyclic-AMP Phosphodiesterases