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- Title
Different Time-Courses of Thermal Nociception in Different Rat Models with Insulin Resistance, Type 2 Diabetes and Hyperinsulinemia.
- Authors
Sugimoto, Kazuhiro; Rashid, Irena B.; Tanabe, Jutaro; Tamasawa, Naoki; Suda, Toshihiro; Shoji, Masaru; Yasujima, Minoru
- Abstract
Predominantly small fiber sensory neuropathy may occur in pre-diabetic and diabetic subjects with metabolic features of insulin resistance (IR), but its etiology and natural history have not been explored. The objective of the present study was to characterize the time-course of thermal nociceptive response, a commonly used measure of small fiber sensory function, in different rat models with IR, type 2 diabetes and hyperinsulinemia. We examined changes in the tail flick latency (TFL) to noxious radiant heat stimulus in 8- to 36-wk-old male obese Zucker rats as a model of obesity-associated IR (n=7∼), in 8- to 36-wk-old male Zucker diabetic fatty (ZDF) rats as a model of type 2 diabetes (n=7∼) and in 10- to 39-wk-old non-diabetic male Wistar rats that continued to receive exogenous insulin (2-4 U/day) via subcutaneously implanted insulin pellets as a hyperinsulinemia rat model (n=∼8), respectively. The findings from the former two models were compared with those from their respective lean littermates (n=6∼), and those from the last model with those from untreated Wistar rats (n=4-8) at each time point examined. The obese Zucker rat model had early-onset, sustained obesity associated with mild hyperglycemia (ca. 10 mmol/1), which was manifested after 10 wks of age. This 1R model developed thermal hyperalgesia indicated by a decrease in the TFL only at 8 wks of age and thermal hypoalgesia indicated by an increase in the TFL after 32 wks of age. The ZDF rat model showed severe hyperglycemia (ca. 20 mmol/1) after 10 wks of age and early-onset obesity, which only persisted up to 14 wks of age as the blood insulin level drops following an initial compensatory hyperinsulinemia in this model. This type 2 diabetes model developed thermal hyperalgesia between 8 wks and 10 wks of age and thermal hypoalgesia after 14 wks of age. The hyperinsulinemia rat model exhibited greater body weight gain after insulin administration with an occasional mild to moderate decrease in blood glucose (no less than 2.4 mmol/l) and developed a temporal thermal hypoalgesia between 22 wks and 26 wks of age. Thus, the time-course of thermal nociception differed in different rat models with IR, type 2 diabetes and hypednsulinemia, From this finding, we conclude that thermal hyperalgesia may occur as an early manifestation of IR, while thermal hypoalgesia may result from either attenuated or increased insulin action on the peripheral nerve in rats.
- Subjects
INSULIN resistance; TYPE 2 diabetes; PREDIABETIC state; NEUROPATHY; HYPERGLYCEMIA; INSULIN; LABORATORY rats
- Publication
Diabetes, 2007, Vol 56, pA208
- ISSN
0012-1797
- Publication type
Article