Goto-Kakizaki (GK) rats_Type II diabetes
Model advantages:
The Goto-Kakizaki (GK) rat model is one of the best characterized animal model of spontaneous type 2 diabetes, generated by selecting and inbreeding hyperglycemic Wistar rats (produced byMetabrain Research). This non-obese diabetic rat presents many similarities with type 2 diabetic patients in term of pancreas dysfunction such as impaired glucose stimulated insulin secretion, reduction in beta-cell mass, perturbed islets microenvironment, and multiple beta-cell functional common defects. Furthermore, it also displays both bladder and sexual dysfunctions, complications commonly associated to diabetes type 2 in patients.Pathophysiological features:
Metabolic features:
- Hyperglycemia
- Defective insulin secretion in response to glucose (figure 1)
- Decreased β cell mass (50%)
- Hepatic and peripheral insulin resistance
- Defects in lipid metabolism (mainly cholesterol)
- Inflammation, particularly in pancreatic islets
Figure 1: Plasma glucose and insulin levels in 18-weeks old GK rats and in age-matched Wistar rats before and 10, 20, 30, 60 and 120 min after oral glucose challenge (2g/kg body weight). (Pelvipharm, internal data).
Cardiovascular features:
- Defective cardiac function (heart hypertrophy, lower heart rate)
- Increased blood pressure
Genito-sexual features:
- Erectile dysfunction (ED), only partially reversed by ED standard-of-care sildenafil (figure 2)
- Hypogonadism
Figure 2: Erectile responses elicited by cavernous nerve stimulation at increasing stimulation frequencies in anaesthetized Wistar rats (treated with saline) and GK rats (treated with saline or with sildenafil 0.3 mg/kg i.v.) reported as intracavernosal pressure/mean arterial pressure rise (ΔICP/MAP). (Pelvipharm, internal data).
Bladder and urinary features:
- Diabetic bladder dysfunction (DBD) with detrusor overactivity, increased bladder capacity and micturition pressure. Bladder contraction parameters reversed by OAB standard-of-care solifenacin (figure 3)
- Proteinuria
Figure 3: Effect of i.v. solifenacin (1 mg/kg) or saline on micturition pressure parameter characterizing micturition contraction in GK rats. (Pelvipharm, internal data).
Links to applicable Experimental skills
- Administration routes / Regimen
- Confocal Microscopy
- Immunohistology
- Metabolic cages (diuresis, renal function, spontaneous micturition)
- Morphology
- Morphometry
- Non invasive blood pressure monitoring (tail cuff)
- Organ bath with animal tissues (In Vitro studies)
- Plasma / urine / tissue collection
- Protein expression and activity
- Spectrophotometric assays
- Telemetry
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