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

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 1st 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 5th
subgroup was considered as the diabetic control (STZ), in addition to 6 normal rats
was used as free control group (C). The 2nd group divided as the same as in 1st 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 1st 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
2nd group (regular form, in the yeast) decrease the level of FBG significantly only at
1st week of treatment, their reduction effect decrease, the severity of hyperglycemia 
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 finding. Conclusion: The
INSUGEAT preps in biphasic form had the more potent effect in management of STZinduced
IDDM and its complications. These effects were pronounced in PC and PPC
preps and to a lesser extend in SP prep.