Clinical Medicine, Physiology

Metabolism and Diabetes

To Conquer Diabetes, Obesity, Metabolic Syndrome and Atherosclerosis:Elucidation of the Mechanisms Maintaining Metabolic Homeostasis at a WHOLE BODY Level

Medical Sciences Course

  • Doctoral Degree



Professor, M.D. Ph.D.

Research Theme

  • Inter-organ neuronal communication achieving metabolic fine-tuning
  • Vascular research for increasing healthy life-spans
  • Clinical studies designed to conquer metabolic diseases in humans
Research Keywords:

inter-organ metabolic communication, dynamic homeostasis of systemic metabolism, pancreatic beta cell regeneration, diabetes, obesity

Technical Keywords:

analyses of systemic glucose metabolism, analyses of systemic energy metabolism, hyperinsulinemic euglycemic clamp, analyses of brain function, inducible tissue-specific knockout mice

Laboratory Introduction

The aim of our research is to conquer metabolic diseases such as diabetes, obesity, metabolic syndrome and atherosclerosis. For this purpose, we strive to elucidate the precise mechanisms whereby multi-organ creatures maintain metabolic homeostasis at a whole body level. We have recently discovered that INTER-ORGAN METABOLIC COMMUNICATION via NEURONAL RELAYS, consisting of afferent and efferent nerves, play important roles in coordinating metabolism in several organs, leading to maintaining dynamic homeostasis at a WHOLE BODY level(Fig.1). For example, increased lipid accumulation in the liver reducesperipheral adiposity via increasedbasal metabolic rates (Science 2006), while increased glucose uptake into the liver suppresses thermogenesis in brown adipose tissue (Cell Metabolism 2012). In addition, hepatic ERK activation promotes pancreatic β cell proliferation (Science 2008) (Fig.2). Based on our original findings, we have proposed that inter-organ communication via neuronal relays achieves METABOLIC FINE-TUNING at the whole body level (Circ Res 2007). Using this system, the brain functions as a conductor coordinating systemic metabolism among many organs. These inter-organ mechanisms constitute potential therapeutic targets for obesity and diabetes by regulating energy expenditure and inducing pancreatic β cell regeneration. Our highest aspiration is for the research we have conducted to develop novel therapies for these common metabolic diseases and senescence by manipulating these inter-organ communication mechanisms.

Figure 1. The inter-organ metabolic communication via neuronal relays

Figure 1. The inter-organ metabolic communication via neuronal relays

Figure 2. Induction of pancreatic β cell proliferation by pancreatic ERK activation

Figure 2. Induction of pancreatic β cell proliferation by pancreatic ERK activation

Recent Publications

  • Uno K, et al. Neuronal pathway from the liver modulates energy expenditure and systemic insulin sensitivity. Science 312(5780): 1656-1659, 2006
  • Imai J, et al. Regulation of pancreatic β cell mass by neuronal signalsfrom the liver. Science 322(5905): 1250-4, 2008
  • Imai J, et al. Eradication of insulin resistance. The Lancet 374: 264, 2009
  • Tsukita S, et al. Hepatic glucokinase modulates obesity predisposition by regulating BAT thermogenesis via neural signals. Cell Metab 16(6): 825-832, 2012
  • Uno K, et al. Ahepatic aminoacid/mTOR/S6K-dependent signaling pathway modulates systemic lipid metabolism via neuronal signals. Nat Commun. 6: 7940, 2015