Acute Euglycemia Restores the Direct Hepatic Effect of Insulin on Glucose Production (GP) in Depancreatized Diabetic Dogs

grantor: University of TorontoIn our previous studies in normal dogs and humans, insulin had both a peripheral extrahepatic effect and a direct effect in suppressing glucose production (GP) whereas the direct effect was undetectable in moderately hyperglycemic diabetic dogs. The purpose of this thesis was to investigate whether euglycemia restores the direct effect of insulin on GP in diabetic dogs. Insulin was infused portally (POR) or peripherally at half the rate (1/2PER) to match the peripheral insulin levels and therefore obtain a selective POR vs. 1/2PER difference in hepatic insulin levels. A greater suppression of GP was seen with POR than 1/2PER during euglycemia. The effect of portal (POR REPL) vs. peripheral basal replacement doses (PER REPL) was also analyzed. To obtain the same basal euglycemia, a greater degree of peripheral insulinemia was required with PER REPL than POR REPL which is also consistent with a direct effect of insulin in suppressing GP. Therefore, acute insulin-induced restoration of euglycemia in diabetic dogs restores the direct hepatic effect of insulin on GP. Our studies show that the physiological route of insulin delivery results in better regulation of GP and in less peripheral hyperinsulinemia than the peripheral route.M.Sc

<span style="font-size: 21.5pt;mso-bidi-font-size:14.5pt;font-family:"Times New Roman","serif"">Identification of amastigote-specific antigens of <i>Leishmania donovani </i>using kala-azar patient sera* </span>

623-628<span style="font-size: 15.5pt;mso-bidi-font-size:8.5pt;font-family:" times="" new="" roman","serif""="">Antigenic characterization of the soluble fraction of axenic amastigotes of Leishmania donovani (strain Dd8, causative agent of Indian kala-azar) and their comparison with promastigotes is reported. The axenic amastigotes were assessed for their immunological status employing anti-A2 monoclonal antibody which is extremely specific for L. donovani amastigotes. SDS-PAGE of 35[S] methionine labeled proteins of the two parasite stages exhibited few stage specific and some conserved antigens in both the stages. An increased synthesis of heat shock proteins was observed in axenic amastigotes. Western blot experiments employing sera of kala azar positive patients identified immunodominent antigens of 116,83,26 and 12 kDa in axenic amastigotes which were not present in promastigotes. These amastigote stage specific antigens may have immense potential in immunodiagnosis and prophylaxis of kala-azar. </span