Enhancement of glucose-induced insulin secretion in transgenic mice overexpressing human VIP gene in pancreatic beta cells.
Using transgenic mice technology, it has now become possible to test directly whether VIP and PHM-27 can enhance glucose-induced insulin secretion and reduce blood glucose in vivo. By microinjecting the entire human VIP gene ligated to the rat insulin II promoter, we have established a mouse model that overproduces VIP and PHM-27 in pancreatic beta cells. VIP was secreted from transgenic islets in a glucose-dependent manner. Analyses of these VIP-transgenic mice indicated that the transgene efficiently enhances glucose-induced insulin secretion and significantly reduces blood glucose as compared with control mice. The transgene also ameliorated glucose intolerance of 70% depancreatized mice. The present results suggest that somatic cell gene therapy directed to diabetic islets by human VIP/PHM-27 gene introduction may provide a means to improve the secretory function of the diabetic islets.
Kato
I
I
Department of Biochemistry, Tohoku University School of Medicine, Miyagi, Japan.
Suzuki
Y
Y
Akabane
A
A
Yonekura
H
H
Tanaka
O
O
Kondo
H
H
Takasawa
S
S
Yoshimoto
T
T
Okamoto
H
H
D000818:Animals; D001786:Blood Glucose / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000628:therapy; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D010451:Peptide PHI / Q000096:biosynthesis; D051381:Rats; D014660:Vasoactive Intestinal Peptide / Q000096:biosynthesis* / Q000235:genetics
D001786:Blood Glucose; D007328:Insulin; D010451:Peptide PHI; D014660:Vasoactive Intestinal Peptide; D005947:Glucose