Research Project
Grant-in-Aid for Scientific Research (B)
In population aging, such as in Japan, it is important to prolong healthy and productive life span. Growth hormone and IGF-I axis (GH-IGF-I axis) is essentially related to the regulation of life span. We have analyzed how GH-IGF-I axis regulates life span using clinical data, animal models and cellular models. The excess status of GH-IGF-I axis model in human is acromegaly. In acromegaly, shortened life span has been reported, although the mechanisms are unknown. We analyzed the effect of an excess IGF-I in cellular models and found that high concentration of IGF-I induces oxidative stress (reactive oxygen spiecies; ROS) in adipocytes and myocytes. Because it is well known that ROS plays an important role in the aging processes so that it is intriguing that IGF-I stimulates ROS production. It is speculated that ROS produced by IGF-I enhances aging changes in many organs. On the other hand, in a human model of lack in GH-IGF-I axis, adult growth hormone deficiency (AGHD), it has been reported that in AGHD patient, based on its metabolic syndrome-like symptoms including visceral obesity, abnormal lipid profile, reduced muscle and bone mineral density, increased non-alcoholic fatty liver disease (NAFLD)/ non-alcoholic steatohepatitis (NASH), premature atherosclerosis and increased risk in mortality are observed. We found that in a patient with NASH and AGHD, GH treatment drastically ameliorates liver dysfunction and liver histological abnormality concomitant with inflammation and oxidative stress. These results imply an important role of GH-IGF-I axis in the metabolic regulation in adult. Further, we found an independent effect of GH from IGF-I on metabolic regulation. It is suggested that GH has direct action and IGF-I-independent regulatory role in metabolism and life span.
All 2008 2007 2006 Other
All Journal Article (66 results) (of which Peer Reviewed: 24 results) Presentation (17 results) Book (7 results)
Molecular and Cellular Endocrinology 280
Pages: 20-29
Regulatory Peptides 138
Pages: 141-144
GASTROENTEROLOGY 132
Pages: 938-943
Endocrine Journal 54(2)
Pages: 239-245
European Journal of Endocrinology 156
Pages: 637-645
European Journal of Endocrinolog 157
Pages: 19-27
Internal Medicine 46
Pages: 1577-1583
Biochemical and Biophysical Research Communications 364
Pages: 1037-1042
日本医事新報 4319
Pages: 9-14
診断と治療 95(2)
Pages: 227-231
ホルモンと臨床 55(4)
Pages: 107-113
ホルモンと臨床 55増刊号
Pages: 3-9
Pages: 126-130
総合臨床 56増刊号
Pages: 723-737
日本内分泌学会雑誌 第17回臨床内分泌代謝Update Proceeding 83(Suppl)
Pages: 96-98
Pages: 174-177
Pages: 158-160
European Journal of Endocrinology 157
Biochemical and Biophysical Research Communications 341
Pages: 88-93
Endocrine Journal 53(1)
Pages: 27-34
Osteoporos Int1 7
Pages: 627-633
Internal Medicine 45
Pages: 265-269
Growth Hormone & IGF Research 16
Pages: 132-142
J Bone Miner Metab 24
Pages: 349-352
Endocrinology 147(5)
Pages: 2583-2590
Hormone and Metabolic Research 38
Pages: 411-416
CURRENT MEDICAL RESEARCH AND OPINION 22(10)
Pages: 1973-1979
Pages: 340-347
Pages: 740-745
Endocrine Journal 53(6)
Pages: 819-827
Endocrine Journal 53(5)
Pages: 699-703
Pages: 853-858
Endocrinology & Diabetes 114
Pages: 599-604
薬の知識 57(1)
Pages: 16-17
日本内分泌学会雑誌 第16回日本間脳下垂体腫傷学会proceeding 82(Suppl)
Pages: 69-71
Pages: 75-78
脳神経外科 34(11)
Pages: 1083-1092
日本医事新報 4297
Pages: 57-62
内分泌・糖尿病科 23(Suppl.3)
Pages: 95-99
日本内分泌学会雑誌 82(Suppl)
Pages: 67-69
最新医学・別冊 新しい診断と治療のABC 43
Pages: 196-207
別冊日本臨床 新領域別症候群シリーズ 3
Pages: 351-354
ホルモンと臨床 54
Pages: 150-155
Molecular Pathogenesis and Therapy of Pituitary Disease, HypoCCS Series Volume 9, 211
Osteoporos Int 17
CURRENT MEDICAL RESEARCH AND OPINION Vol. 22, No. 10
Growth Hormone&IGF Research 16
