Sensory and motor physiological functions are impaired in gastric inhibitory polypeptide receptor-deficient mice.
OBJECTIVE
Gastric inhibitory polypeptide (GIP) is an incretin secreted from the gastrointestinal tract after an ingestion of nutrients, and stimulates an insulin secretion from the pancreatic islets. Additionally, GIP has important roles in extrapancreatic tissues: fat accumulation in adipose tissue, neuroprotective effects in the central nervous system and an inhibition of bone resorption. In the current study, we investigated the effects of GIP signaling on the peripheral nervous system (PNS).


METHODS
First, the presence of the GIP receptor (GIPR) in mouse dorsal root ganglion (DRG) was evaluated utilizing immunohistochemical analysis, western blotting and reverse transcription polymerase chain reaction. DRG neurons of male wild-type mice (WT) were cultured with or without GIP, and their neurite lengths were quantified. Functions of the PNS were evaluated in GIPR-deficient mice (gipr-/-) and WT by using current perception thresholds (CPTs), Thermal Plantar Test (TPT), and motor (MNCV) and sensory nerve conduction velocity (SNCV, respectively). Sciatic nerve blood flow (SNBF) and plantar skin blood flow (PSBF) were also evaluated.


RESULTS
We confirmed the expression of GIPR in DRG neurons. The neurite outgrowths of DRG neurons were promoted by the GIP administrations. The gipr-/- showed impaired perception functions in the examination of CPTs and TPT. Both MNCV and SNCV were delayed in gipr-/- compared with these in WT. There was no difference in SNBF and PSBF between WT and gipr-/-.


CONCLUSIONS
Our findings show that the GIP signal could exert direct physiological roles in the PNS, which might be directly exerted on the PNS.
Department of Endocrinology and Diabetes Nagoya University Graduate School of Medicine Nagoya Japan.
Tetsuji
T
Okawa
Department of Chronic Kidney Disease Initiatives Nagoya University Graduate School of Medicine Nagoya Japan.
Hideki
H
Kamiya
Department of Endocrinology and Diabetes Nagoya University Graduate School of Medicine Nagoya Japan.
Tatsuhito
T
Himeno
Department of Metabolic Medicine Nagoya University School of Medicine Nagoya Japan.
Yusuke
Y
Seino
Department of Endocrinology and Diabetes Nagoya University Graduate School of Medicine Nagoya Japan.
Shin
S
Tsunekawa
Department of Genetics Research Institute of Environmental Medicine Nagoya University Nagoya Japan.
Yoshitaka
Y
Hayashi
Department of Diabetes and Clinical Nutrition Kyoto University Graduate School of Medicine Kyoto Japan.
Norio
N
Harada
Department of Endocrinology Diabetes and Geriatric Medicine Akita University Graduate School of Medicine Akita Japan.
Yuichiro
Y
Yamada
Department of Diabetes and Clinical Nutrition Kyoto University Graduate School of Medicine Kyoto Japan.
Nobuya
N
Inagaki
Kansai Electric Power Hospital Osaka Japan.
Yutaka
Y
Seino
Department of Endocrinology and Diabetes Nagoya University Graduate School of Medicine Nagoya Japan.
Yutaka
Y
Oiso
Department of Endocrinology and Diabetes Nagoya University Graduate School of Medicine Nagoya Japan.
Jiro
J
Nakamura
Gastric inhibitory polypeptide; Incretins; Peripheral nervous system