Time course of pain sensation in rat models of insulin resistance, type 2 diabetes, and exogenous hyperinsulinaemia.
BACKGROUND
Small sensory fibre dysfunction has been recently recognized as a component of impaired glucose tolerance and insulin resistance (IR) syndrome. However, few studies have investigated whether small sensory fibre dysfunction develops in normoglycaemic or pre-diabetic animal models of IR and/or hyperinsulinaemia. In addition, scant information is available on the metabolic features of IR in relation to small sensory fibre dysfunction due to the progressive failure of beta cells to compensate for IR during the development of frank diabetes.


METHODS
Longitudinal trends for thermal and mechanical nociceptive responses were assessed in 8-36-week-old male obese Zucker rats, 8-36-week-old male Zucker diabetic fatty (ZDF) rats, and 10-39-week-old male Wistar rats that continued to receive exogenous insulin (2-4 U/day) from subcutaneously implanted insulin pellets. Data were compared with the metabolic disorders in these rats.


RESULTS
Both obese Zucker and ZDF rats at 8 weeks of age showed compensatory hyperinsulinaemia and developed thermal hyperalgesia prior to the onset of overt hyperglycaemia. These animals also exhibited progression from thermal hyperalgesia to hypoalgesia, which occurred more rapidly and coincided with a more rapid decline in pancreatic insulin secretion in ZDF rats than in obese Zucker rats. Non-diabetic rats treated with insulin tended to show thermal and mechanical hypoalgesia that was detectable 12-20 weeks after treatment.


CONCLUSIONS
In addition to insulin treatment, IR with or without compensatory hyperinsulinaemia is associated with nociceptive dysfunction of different phenotypes, independent of glycaemic levels.
Sugimoto
Kazuhiro
K
Department of Laboratory Medicine, Hirosaki University Graduate School of Medicine, Zaifu-cho, Hirosaki, Japan. sugimoto@cc.hirosaki-u.ac.jp <sugimoto@cc.hirosaki-u.ac.jp>
Rashid
Irena B
IB
Kojima
Keiya
K
Shoji
Masaru
M
Tanabe
Jutaro
J
Tamasawa
Naoki
N
Suda
Toshihiro
T
Yasujima
Minoru
M
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D006943:Hyperglycemia / Q000097:blood; D006946:Hyperinsulinism / Q000503:physiopathology*; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D009765:Obesity / Q000503:physiopathology; D010146:Pain / Q000503:physiopathology*; D010147:Pain Measurement; D051381:Rats; D011924:Rats, Zucker; D013851:Thinness / Q000503:physiopathology
D001786:Blood Glucose