Comparative Study of Different Preparations of Recombinant Insulin from Yeast Cells on STZ-Induced Insulin Dependent Diabetes Mellitus in Albino Rats

Abstract

Background: This study is used to compare the effects between three different INSUGEAST preparations (preps) (recombinant insulin from yeast cells) in management of insulin dependent diabetes mellitus (IDDM) and its complications. The preps were extracted from modified genetically saccharomyces cerviciae on culture pure camel milk (PC), partial pure camel milk (PPC) and specific media (SP) parallel with insulin stander (ST). Also the study extended to evaluate the difference in effect of the aforementioned INSUGEAST preps in three forms, regular, biphasic and recombinant in yeast cells against the stability and severity of hyperglycemia. Method: IDDM was induced in female albino rats by intraperitoneal injection (i.p) of a single dose 70mg/kg/B.wt of streptozotocin (STZ) in citrate buffer. The diabetic rats were classified into two groups; the 1 st group divided into 5 equal subgroups, four subgroups, each was injected subcutaneously (s.c) by PC, PPC, SP and St respectively, in the biphasic form, in a dose of 4.2 IU/kg/B.wt for 3weeks.The 5 th subgroup was considered as the diabetic control (STZ), in addition to 6 normal rats was used as free control group (C). The 2 nd group divided as the same as in 1 st group but the INSUGEAST preps used involve little protamine zinc or in the regular form in addition to other 2 subgroups, each of them treated orally either with an amount of yeast (Y) containing insulin equivalent to 4.2 IU/kg/B.wt or added to it specific additive (YA) and treated for the same period. Blood glucose level either fasting (FBG) or after 2h from glucose and insulin loading were measured weekly for all groups. Biochemical assays to ascertain diabetic complications resemble in hepatorenal dysfunction included: aminotransferase aspartate (AST) and alanate (ALT), alkaline phosphatase (ALP), creatinine (Creat) and blood urea nitrogen (BUN); hyperlipidemia indicators included: total cholesterol (T-Ch), low density lipoprotein cholesterol (LDL-Ch), high density lipoprotein cholesterol (HDL-Ch) and triglycerides (TG) were measured at the end of the experimental schedule. The result of this study showed that: 1-Blood glucose level in 1 st group was markedly decreased after insulin injection in all different preps and similar to the effect of insulin standard. 2-The hepato-renal dysfunction and hyperlipidemea induced by STZ injection, showed significant improvements after INSUGEAST preps (biphasic form), especially with insulin prepared on PPC and PC media. 3-INSUGEAST preps on the 2 nd group (regular form, in the yeast) decrease the level of FBG significantly only at 1 st week of treatment, their reduction effect decrease, the severity of hyperglycemia Bull. Egypt. Soc. Physiol. Sci. 31 (2) 2011 Elsisi & Elgamal 104 increase, animals could not survive and mortality rate increase 4-The diabetic complications (hepato-renal dysfunction, hyperlipidemia) increased in all groups of this part and not showed any improvements. 5-Histopathological study made on pancreas, liver and kidney tissues conform the present ...