Time course of pain sensation in rat models of insulin resistance, type 2 diabetes, and exogenous hyperinsulinaemia

Abstract

In addition to insulin treatment, IR with or without compensatory hyperinsulinaemia is associated with nociceptive dysfunction of different phenotypes, independent of glycaemic levels.

Pioglitazone Inhibits the Development of Hyperalgesia and Sensitization of Spinal Nociresponsive Neurons in Type 2 Diabetes

“…Consistent with previous reports, ZDFs developed mechanical 6, 25, 49, 69, 78, 80, 92, 101, 112 , heat 25, 49, 78, 80 , and cold hyperalgesia 80 at 14 to 18 wks of age 25, 69, 101 , results which we replicated in two separate cohorts. In contrast, a comparatively small number of ZDF studies report either mechanical hypoalgesia 89 , heat hypoalgesia 89, 92, 101 , no difference in heat 6 or pressure 73 response thresholds, and/or pressure hyperalgesia prior to hyperglycemia 79 .…”

“…When compared to control heterozygotes or wild-types, only ZDF rats homozygous for the fatty (fa/fa) leptin receptor mutation develop cardinal symptoms of glucose-intolerant diabetes 13 including hyperphagia 69,83 , hyperinsulinemia 51, 65, 92 , obesity 69 , hyperglycemia 69, 73, 101 , elevated HbA1c 51, 92 , and increased MG-AGE 89 . In the first experiment we characterized the progression of hyperglycemia and pain-like behavior in diabetic ZDF and control ZL rats.…”

“…However, conflicting studies report either hypoalgesia 89, 92 or hyperalgesia 78, 112 in similarly aged ZDF. This raises concerns regarding examination of sensory thresholds at just a single age without regard to the developmental stage of diabetes 6, 49, 78, 89, 112 , or omission of ZL controls when multiple ages are assessed 69 .…”

“…Hyperglycemia develops within 6–10 wks of age 6, 13, 49, 92 in ZDF but not Zucker Lean (ZL fa/+ ) controls, and is followed by behavioral correlates of PDN, including hypersensitivity to mechanical 6, 25, 69, 78, 92, 101, 112 and thermal 25, 49, 78, 80 somatosensory stimulation. However, conflicting studies report either hypoalgesia 89, 92 or hyperalgesia 78, 112 in similarly aged ZDF.…”

KGA-2727, a Novel Selective Inhibitor of a High-Affinity Sodium Glucose Cotransporter (SGLT1), Exhibits Antidiabetic Efficacy in Rodent Models

“…Hyperglycemia causes progressive damage to pancreatic ␤-cells through endoplasmic reticulum stress and oxidative stress and consequently diminishes insulin secretion (Robertson et al, 2003;Prentki and Nolan, 2006;Eizirik et al, 2008). The blood insulin level in the ZDF rat increases to compensate for insulin resistance until 10 weeks of age and then decreases along with the progressive dysfunction of pancreatic ␤-cells (Sugimoto et al, 2008). Several studies have shown that jpet.aspetjournals.org pharmacological treatment to control hyperglycemia results in preservation of pancreatic ␤-cells in rodent models (Koyama et al, 2000;Fukaya et al, 2009).…”