Adenovirus-mediated insulin gene transfer improves nutritional and post-hepatectomized conditions in diabetic rats.
BACKGROUND
Impaired nutritional conditions in patients with diabetes are significant risk factors after major abdominal surgery. We constructed recombinant adenovirus vector carrying the human insulin gene (AxCAIns) for in vivo insulin gene transfer to improve metabolic impairments after a major operation in patients with diabetes. We tested the effects of AxCAIns on nutritional and post-hepatectomized conditions in rats with diabetes treated with streptozotocin (STZ).


METHODS
AxCAIns was injected into the spleen in diabetic rats treated with STZ. Blood levels of glucose, total protein, albumin, and C-peptide of human proinsulin were measured and the expression of transferred human insulin gene was analyzed in various organs. Diabetic rats underwent 70% partial hepatectomy with or without AxCAIns injection, and post-hepatectomized conditions were analyzed.


RESULTS
STZ-induced hyperglycemia was reduced by AxCAIns injection. Decreased serum levels of total protein and albumin in diabetic rats were significantly restored to normal levels by AxCAIns injection, and human C-peptide was detected in the sera of AxCAIns-treated rats. Human preproinsulin messenger RNA, which represented the expression of transferred insulin gene, was detected in the liver and the spleen, but not in other organs. Serum albumin levels, remnant liver weight, and ratios of postoperative body weight to preoperative body weight were significantly increased by AxCAIns in hepatectomized diabetic rats.


CONCLUSIONS
AxCAIns injection to the spleen efficiently transferred the human insulin gene mainly into the hepatocytes and produced enough human proinsulin to improve nutritional impairments and post-hepatectomized conditions in diabetic rats. Insulin gene transfer with intrasplenic injection of AxCAIns may be available to improve metabolic impairment after major abdominal surgery in patients with diabetes.
Yamaguchi
M
M
Department of Surgery, Showa University Fujigaoka Hospital, Yokohama, Japan.
Kuzume
M
M
Matsumoto
T
T
Shimura
H
H
Matsumiya
A
A
Nakano
H
H
Takeda
M
M
Sanada
Y
Y
Kumada
K
K
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006498:Hepatectomy; D006801:Humans; D007328:Insulin / Q000235:genetics*; D007763:Lac Operon; D008099:Liver / Q000378:metabolism; D009752:Nutritional Status; D011384:Proinsulin / Q000235:genetics; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection
D017931:DNA Primers; D007328:Insulin; D011498:Protein Precursors; D012333:RNA, Messenger; C013737:preproinsulin; D011384:Proinsulin