Table 1.
The anti-hyperglycaemic effects of CQ and HCQ in animal studies
| Types of animal | Types of induction | Treatment, dose, route and duration | Research outcomes | Mechanism of action | Reference |
|---|---|---|---|---|---|
| Female Sprague-Dawley rats | STZ (50 mg/kg, i.v.) | CQ (20 mg/kg, twice weekly, i.m., 12 weeks) | FBG: ↓, HbA1c: ↓, glycated plasma protein: ↓, insulin: ↑ | - | 21 |
| - | CQ (20 mg/kg, thrice weekly, i.m., 20 weeks) | FBG: ↓, HbA1c: ↓, insulin: ↑ | - | ||
| Adult male Sprague-Dawley rats | STZ (60 mg/kg, i.p.) | HCQ (80, 120 or 160 mg/kg/day, oral, 10 days) | Glucose: ↓ | - | 22 |
| - | HCQ (160 mg/kg/day, oral, 10 days | FBG: ↔ | - | ||
| Adult Sprague-Dawley rats | STZ (27.5 mg/kg, i.p.) | HCQ (200 mg/kg/week, oral, 4 weeks) | FBG: ↓, OGTT: ↓, insulin: ↑, β-cell function: ↑ | IL-1β: ↓, IL-6: ↓, TNF-α: ↓, TGF-β1: ↓, MCP-1: ↓, IL-10: ↔, caspase-3: ↓, Bcl-2: ↑ | 23 |
| Male C57BL mice | STZ (60 mg/kg, i.p.) | CQ (60 mg/kg/day, i.p., 14 days) | Glucose: ↔ | LC3-II: ↑, p62: ↑, Beclin1: ↔, autophagic vacuoles: ↓ | 24 |
| Male Wistar rats | Alloxan monohydrate (90 mg/kg, i.p.) | HCQ (200 mg/kg/day, oral, 9 days) | Glucose: ↓ | - | 26 |
| Male Wistar rats | High-fat diet (35% lard) | CQ (3.5 mg/kg, twice per week, i.p., 1 month) | Glucose uptake in muscle cells: ↑ | p-Akt: ↑, p-JNK: ↔, p-GSK3β: ↑, glycogen synthase activity: ↑ | 27 |
| Adult Sprague-Dawley rats | High-fat diet (46% fat, 20.3% protein, 24% carbohydrate) | HCQ (6.5 mg/kg/day, oral, 12 weeks) | FBG: ↓, OGTT: ↓, insulin: ↓, HOMA-IR: ↓, β-cell function: ↑ | E-selectin: ↓, ICAM-1: ↓, VCAM-1: ↓, leptin: ↓, resistin: ↓, visfatin: ↓, adiponectin: ↑, lipocalin-2: ↓ | 28 |
| Male C57BL/6J mice | High-fat diet (60% fat) | HCQ (40 mg/kg/day, pre-treatment, i.p., 17 weeks) | IPGTT: ↓, insulin: ↓, ITT: ↓, HOMA-IR: ↓, HOMA-IS: ↑, glucose uptake in HepG2 cells: ↑ | IL-1β: ↓, IL-6: ↓, TNF-α: ↓, MCP-1: ↓, CD68: ↓, Arg1: ↓, p-Akt: ↑, p-IRS1: ↑ | 29 |
| Male db/db mice | - | HCQ (50 mg/kg/day, oral, 7 days) | Insulin: ↑, glucose: ↔ | IGF-1: ↔, p-Akt: ↑, p-mTOR: ↔, p-S6: ↔ | 30 |
Abbreviations: Arg1, arginase 1; Bcl-2, B-cell lymphoma 2; CD, cluster of differentiation; CQ, chloroquine; FBG, fasting blood glucose; HbA1c, glycated haemoglobin; HCQ, hydroxychloroquine; HepG2, human liver cancer cell line; HOMA-IR, homeostatic model assessment for insulin resistance; HOMA-IS, homeostatic model assessment for insulin sensitivity; ICAM-1, intercellular adhesion molecule 1; IGF-1, insulin growth factor 1; IL-1β, interleukin-1 beta; IL-6, interleukin-6; IL-10, interleukin-10; i.m., intramuscular; i.p., intraperitoneal; IPGTT, intraperitoneal glucose tolerance test; ITT, insulin tolerance test; MCP-1, monocyte chemoattractant protein-1; OGTT, oral glucose tolerance test; p-Akt, phosphorylated protein kinase B; p-GSK3β, phosphorylated glycogen synthase kinase-3 beta; p-IRS1, phosphorylated insulin receptor substrate 1; p-JNK, phosphorylated c-Jun N-terminal kinase; p-mTOR, phosphorylated mammalian target of rapamycin; STZ, streptozotocin; TC, total cholesterol; TG, triglyceride; TGF-β1, transforming growth factor-beta 1; TNF-α, tumour necrosis factor-alpha; VCAM-1, vascular cell adhesion molecule 1; ↑, increase/stimulate; ↓, decrease/inhibit; ↔, no change.