Central nervous system and peripheral abnormalities: clues to the understanding of obesity and NIDDM
Diabetologia
Bernard Jeanrenaud Minkowski Award 0 1
Warsaw 0 1
0 Bernard Jeanrenaud was born in La Chaux-de-Fonds (Canton of Neuch~tel), Switzerland. He studied medicine at the Neuchfitel and Geneva Universities, Switzerland. Immediately after his M.D. degree, he went to the USA. He was successively Intern at the Mount Auburn Hospital , Cambridge, Mass. , USA; Assistant in Medicine at the Peter Bent Brigham Hospital and Research Fellow in Medicine at Harvard Medical School , Boston , Mass.; Guest Investigator and Assistant Physician at the Rockefeller University , New York , N.Y. He returned to Switzerland in 1960, to be Assistant in Medicine at the "Clinique Universitaire de Th6rapeutigue", Geneva University Hospital, then Instructor at the "Institut de Biochimie Clinique", Geneva University. H e has long been interested in pathophysiological problems, metabolism, endocrinology, and neuroendocrinology. At one point during his career he had to decide between clinical medicine or fundamental research and he chose the latter. He became, in 1970, Professor at the University of Geneva Faculty of Medicine and Head of the "Laboratories de Recherches Mdtaboliques". His collaborative research deals with experimental endocrinology, experimental diabetes in animals (Type 1 and Type 2 diabetes). He and his colleagues have published about 320 articles in various reputable journals. Bernard Jeanrenaud has always been interested in the practical therapeutic relevance of the experimental work carried out by his team, therefore he has been keen to establish and maintain a relationship with the Industry. The work of his laboratory has been supported by several Foundations, the "D6partment de I' Instruction publique of the State of Geneva"; the Swiss National Research Council and by grants-in-aid from, principally, Nest16 S.A. (Switzerland); Eli Lilly and Company , Indianapolis, Ind. , (USA); the "Institut de Recherches Internationales Servier , I. R. I. S, ,, Paris , (France); the Foundation Ernst et Lucie Schmidheiny, Geneva (Switzerland); the "Commission pour l'encouragement de la recherche scientifique", Berne (Switzerland); and the Foundation Lord Michelham of Hellingly , Geneva , (Switzerland). Bernard Jeanrenaud is an active member of several scientific societies or associations, the European Association for the Study of Diabetes, the European Association for the Study of Obesity, the American Diabetes Association, the European Neuroscience Association, the Endocrine Society, the Biochemical Society, the American Physiological Society, la Soci6t6 de Neuroendo- Diabetes Society (1983) and was Fellow (1983) of the Japanese Society for the Promotion of Science. In 1990 he was awarded the H. E. Wertheimer Prize and Medal by the International Association for the Study of Obesity , of which he became (1990-1994) President
1 Laboratoires de Recherches M6taboliques, Faculty of Medicine, University of Geneva , Geneva , Switzerland
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9 Springer-Verlag1994
Central nervous system and peripheral abnormalities:
clues to the understanding of obesity and NIDDM
Summary To study the impact on glucose handling of
the observed hyperinsulinaemia and hypercorticism
of the genetically obese fa/fa rats, simplified animal
models were used. In the first model, normal rats
were exposed to hyperinsulinaemia for 4 days and
compared to saline-infused controls. At the end of
this experimental period, the acute effect of insulin
was assessed during euglycaemic-hyperinsulinaemic
clamps. White adipose tissue lipogenic activity was
m u c h m o r e insulin responsive in the "insulinized"
than in the control groups. Conversely muscles from
"insulinized" rats became insulin resistant. Such
divergent consequences of prior "insulinization" on
white adipose tissue and muscle were corroborated
by similar divergent changes in glucose transporter
( G L U T 4) m R N A and protein levels in these
respective tissues. In the second model, normal rats were
exposed to stress levels of corticosterone for 2 days. This
resulted in an insulin resistance of all muscle types
that was due to an increased glucose-fatty acid cycle,
without measurable alteration of the G L U T 4
sysThe concept that obesity syndromes in animals, at
least in some, are due to central nervous system
abnormalities, originates from the observation that
lesions of the ventromediat hypothalamic area (VMH)
in normal rats p r o d u c e hormonal and metabolic
disorders that are similar to those observed in
genetically obese rodents [
1-34
]. From this research,
summarized inTable 1, it was concluded for both animal
models of obesity (i.e. hypothalamic obesity obtained by
lesion of the V M H or genetic obesity), that the main
initial defect(s) appeared to be an abnormal central
nervous system regulation of the autonomic nervous
system. It was striking to observe, in particular, that
hyperinsulinaemia both in genetically preobese rats
or in acutely VMH-lesioned rats occurred early and
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