1 Streptozotocin-induced diabetic rats (Wistar) were implanted with sustained release insulin pellets (release rate =4 u day-') or with placebo pellets (palmitic acid) from the onset of glycosuria. 2 Noradrenaline sensitivity, endothelium-dependent relaxation to acetylcholine and endotheliumindependent relaxation to sodium nitroprusside were assessed in mesenteric resistance arteries from the insulin-treated (IT) diabetic animals and compared to placebo-implanted (PI) diabetics and age-matched controls. 3 Arteries from PI-diabetic rats (8-10 weeks) demonstrated an enhanced maximal response to noradrenaline compared to controls, which was not prevented by insulin treatment (control 2.65 ± 0.17 mN mm'1, n = 18 arteries versus PI-diabetic 3.73 ± 0.40 mN mm-', n = 5, P <0.05; control versus IT-diabetic 4.02 ± 0.19 mN mm' , n = 22, P <0.001). Sensitivity to noradrenaline was similar between the three groups. 4 In the presence of the nitric oxide synthase inhibitor N0-nitro-L-arginine methyl ester (L-NAME), IT and PI arteries were more sensitive to noradrenaline than control arteries (pECm: control 5.75 0.08, n = 17, versus PI-diabetic 6.14 ± 0.09, n = 8, P <0.05; control versus IT-diabetic 6.38 ± 0.08, n = 20, P <0.001). 5 The maximum contractile response to depolarizing 125 mM K+ was significantly enhanced in IT-diabetic arteries but not PI-diabetic when compared to control arteries (maximum response: control 3.74±0.15mNmm-', n = 18, versus PI-diabetic 3.61 ±0.19mNmmnr, n = 11, NS; control versus IT-diabetic 4.66 ± 0.18 mN mm-', n = 22, P <0.001). 6 Endothelium-dependent relaxation to acetylcholine was profoundly impaired in the PI-diabetic arteries, but in the IT-diabetic arteries was not significantly different from controls (pECm: control 7.64 0.19, n = 17, versus PI-diabetic 6.07 ± 0.12, n = 8, P <0.001; control versus IT-diabetic 7.36 0.09, n = 22, NS). 7 Endothelium-independent relaxation to sodium nitroprusside was slightly but significantly impaired in the PI-diabetic arteries, but was not significantly different in the IT-diabetic arteries compared to controls (pEC50: control 7.78 ± 0.10, n = 13, versus PI-diabetic 7.31 ± 0.13, n = 13, P <0.05; control, versus IT-diabetic 7.64 ± 0.09, n = 16, NS).

Placental transfer of lactate, glucose and 2-deoxyglucose was examined employing the in situ perfused placenta. Control and streptozotocin induced diabetic Wistar rats were infused with [U14C]-glucose and [3H]-2-deoxyglucose (2DG). The fetal side of the placenta was perfuseci with a cell free medium and glucose uptake was calculated in the adjacent fetuses. Despite the 5-fold higher maternal plasma glucose concentration in the diabetic dams the calculated fetal glucose metabolic index was not significantly different between the 2 groups. Placental blood flow was reduced in the diabetic animals compared with controls but reduction of transfer of [U14C]-glucose and [3H]-2-deoxyglucose and endogenously derived [14C]-Lactate to the fetal compartment, could not be accounted for by reduced placental blood flow alone. There was no significant net production or uptake of lactate into the perfusion medium that had perfused the fetal side of the placenta in either group. The plasma lactate levels in the fetuses adjacent to the perfused placenta were found to be higher than in the maternal plasma and significantly higher in the fetuses of the diabetic group compared with control group. In this model the in situ perfused placenta does not secrete significant quantities of lactate into the fetal compartment in either the control or diabetic group.