Table 2.
Summary of procedures used to reproduce the HAAF phenomenon in rodents.
| Species | Route of administration | Insulin dose used to induce antecedent hypoglycaemia | Insulin dose used to induce subsequent hypoglycaemia | Fasting condition | Blood glucose measurement (method of sampling and assay) | Depth and duration of antecedent hypoglycaemia | Number of antecedent hypoglycaemic episodes | Plasma adrenaline in response to antecedent/subsequent hypoglycaemia (in pg/mL) and method of assay | |
|---|---|---|---|---|---|---|---|---|---|
| Nondiabetic rats | Sprague-Dawley rats [28–41] Wistar rats [42–44] |
s.c [28, 29, 32] i.v [35, 36, 39, 40, 42–44] s.c and i.v [37] i.p and i.v [30, 31, 33, 34, 41] |
1–3 U/kg [28, 30, 32, 37, 38, 40, 42, 43] 5–10 U/kg [31, 33, 34, 39, 41, 44] 12 U/kg [29] 4 U/kg and additional 0.5–1 U/kg [35] 10 U/kg and 6–8 U/kg [36] |
1–3 U/kg [28, 40, 42] 5–10 U/kg [28, 35, 36, 43, 44] 12 U/kg [29] 20–50 mU/kg/min [30, 31, 33, 34, 38, 41] 0.75 U/kg followed by 1.8 U/kg/hr [37] 0.75 U/kg 3 times at 5 min interval [35] |
Fasted overnight [33] Nonfasted [28, 29, 31, 36, 37, 39–44] Overnight prior to subsequent hypoglycaemia [30, 34, 35, 38] Fasted for four hours prior to subsequent hypoglycaemia [32] |
Tail [32, 34, 40] Systemic [28, 30, 35, 39, 41–44] Tail/systemic [31, 36–38] Trunk [29] Glucometer [30, 32, 36, 40] Glucose oxidase method [28, 29, 33–39, 42, 43] Modified Trinder's reaction assay [44] |
1.4–1.9 mmol/L [28, 31, 35, 37, 39, 42, 43] 2–3.2 mmol/L [30, 32–34, 36, 38, 40] 1-2 hrs [28, 31, 32, 35, 37, 39, 40, 42–44] 3 hrs [30, 33, 34, 36, 38, 41] Depth and duration not given [29] |
1/day for 1 day [33, 35, 39] 1/day for 2 days [37] 1/day for 3-4 days [29, 31, 32, 34, 36, 40, 41] 2/day for 1 day [28, 42–44] 2/day for 2 days and 1/day on third day [30, 38] |
450–1000/175–460; p < 0.05–0.01 [28, 32, 36] 1000–3000/740–1500; p < 0.05–0.01 [30, 37–40, 43] 3000–5000/1500–2400; p < 0.05–0.01 [31, 33–35, 41, 42] 1600/1000; p > 0.05 [44] 3800/3250; p > 0.05 [29] HPLC [31–35, 37, 39–41] RIA [28, 42–44] ELISA [29, 30, 36, 38] |
|
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| Diabetic rats | Streptozotocin-induced diabetic Sprague-Dawley rats [45, 46] | i.p [45] s.c and i.v [46] |
6–10 U/kg [45] 2 U/kg [46] |
6–10 U/kg [45] 10 mU/kg/min [46] |
Nonfasted [45] Overnight prior to subsequent hypoglycaemia [46] |
Not given [45] Systemic [46] Glucose oxidase method [45, 46] |
2.8 mmol/L [45] 2.2 mmol/L [46] 3 hrs [45] 1 hr [46] |
1/day for 3 days [45] 2/day for 3 days and 1/day on 4th day [46] |
3010/890; p < 0.05 [45] 5076/5076; p > 0.05 [46] HPLC [45] RIA [46] |
|
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| Nondiabetic mice | C57BL/6 [47, 48] | i.p [48] i.v [47] |
2.5 U/kg [48] 20 mU/kg/min [47] |
2.5 U/kg [48] 20 mU/kg/min [47] |
3 hours prior to injections on all days [48] 6 hours prior to each episode [47] |
Tail [48] Systemic [47] Glucometer [47, 48] |
2.2 mmol/L [48] 3.8 mmol/L [47] 3 hrs [48] 2 hrs [47] |
1/day for 4 days [48] 1/day for 1 day [47] |
14000/15000; p > 0.05 [48] 220/120; p > 0.05 [47] HPLC [47] ELISA [48] |
RIA: radioimmunoassay; HPLC: high-performance liquid chromatography; ELISA: enzyme linked immunosorbent assay.