Table 1.
Effects of L-arginine in the treatment of carbohydrate metabolism disorders.
| Cell Testing | ||||||
| Study (Year) | Cell Line/Model |
Dose(s) of
L-Arginine Tested |
Control Culture | Outcome | ||
| Adeghate et al. (2001) [54] | pancreas fragments of diabetic rats |
100 mM | + | L-arginine stimulates insulin secretion | ||
| Pi et al. (2012) [55] | pancreatic islets of Gprc6a−/− mice | 10 mM | + | L-arginine stimulates insulin secretion in β-cells through GPRC6A activation of cAMP pathways | ||
| Smajilovic et al. (2013) [56] | pancreatic islets of Gprc6a−/− mice | 20 mM | + | L-arginine induces insulin secretion, but GPRC6A is not involved in the process | ||
| Krause et al. (2011) [57] | BRIN-BD11 | 0.1, 0.25, 1.15 mM | + | L-arginine induces insulin secretion, contributes to glutathione synthesis and has a protective effects in the presence of proinflammatory cytokines | ||
| Tsugawa et al. (2019) [58] | Hep G2 | 1, 3.3, 10 mM | + | L-arginine increase IGF-1 level by stimulating of growth hormone secretion | ||
| Cho et al. (2020) [59] | NIT-1 + HEK293FT | 0.1, 0.2, 0.6, 1, 2 mM | + | L-arginine induces insulin secretion due to UGGT1 regulatory functions | ||
| Animal Testing | ||||||
| Study, Year |
Duration
of Experiment |
Dose(s) of
L-Arginine Tested |
Control
Group |
Number
of Animals per Group |
Animal
Model |
Outcome |
| Smajilovic et al. (2013) [56] | 1 min | 0.05 g/kg bw intravenously + 1 g/kg bw orally |
+ | 6–10 | Gprc6a−/− mice | Increase in insulin secretion after intravenous injection and oral administration of L-arginine |
| Tsugawa et al. (2019) [58] | 120 min | 3 mg/kg bw orally | + | 4 | C57BL/6J mice | L-arginine induces secretion of growth hormone and IGF-1 |
| Cho et al. (2020) [59] | 120 min | 0.75, 1.5, 3 mg/g intraperitoneally | + | - | β cell-specific UGGT1-transgenic mice |
UGGT1 mediated proinsulin management regulates insulin secretion |
| Kohli et al. (2004) [60] | 2 weeks | 0.64% in diet + 1.25% in water | + | 8 | Sprague-Dawley rats | L-arginine stimulates endothelial NO synthesis by increasing BH4 concentration, increased insulin concentration in the blood and reduced blood glucose level in diabetic rats |
| Fu et al. (2005) [61] | 10 weeks | 1.44% in diet + 1.25% in water | + | 6 | Zucker diabetic fatty rats | L-arginine increases NO synthesis, lower glucose level and reduce body weight in obese and type 2 diabetic rats |
| Clemmensen et al. (2013) [62] | 15/120 min | 1 g/kg bw orally | + | 7–17 | C57BL/6 mice + Glp1r−/− mice | L-arginine increases GLP-1 and insulin levels and improves glucose clearance in obese mice; effects depends on GLP-1R-signaling |
| El-Missiry et al. (2004) [63] | 1 week | 100 mg/kg bw intragastrically | + | 6–8 | Wistar rats | L-arginine lowers serum glucose and oxidative stress in diabetic rats |
| Ortiz et al. (2013) [64] | 4 days | 622 mg/kg bw/day in water |
+ | 5 | Wistar rats | L-arginine ameliorates oxidative stress and the decrease in NO production in diabetic rats |
| Pai et al. (2010) [65] | 8 weeks | 1.5 g/kg bw/day orally | + | 6–13 | Wistar rats | L-arginine has no effect on plasma glucose levels, but decreases advanced glycation endproducts in diabetic rats |
| Human Research | ||||||
| Study, Year |
Duration
of Experiment |
Dose(s) of
L-Arginine Tested |
Control
Group |
Number
of Subjects per Group |
Outcome | |
| Wascher et al. (1997) [66] | - | 0.52 mg/kg−1 bw/ min−1 (concomitant infusion) |
+ | 7–9 | L-arginine improves insulin sensitivity and restores vasodilatation (insulin-mediated) in obese and non-insulin-dependent diabetic patients; no effects was observed on insulin or IGF-1 levels | |
| Piatti et al. (2001) [67] | 3 months (1 month of intervention) | 3 × 3 g/day orally | + | 12–40 | L-arginine normalizes cGMP levels, improves glucose disposal and systolic blood pressure; the treatment attenuates insulin resistance in type 2 diabetic patients | |
| Lucotti et al. (2006) [68] | 3 weeks | 8.3 g/day orally | + | 16–17 | L-arginine positively affects glucose metabolism and insulin sensitivity, improves endothelial function, oxidative stress, and adipokine release in obese type 2 diabetic patients | |
| Lucotti et al. (2009) [69] | 6 months | 6.4 g/day orally | + | 32 | L-arginine regulates endothelial dysfunction, improves insulin sensitivity and reduces inflammation | |
| Bogdański et al. (2012) [70] | 3 months | 3 × 9 g/day orally | + | 20 | L-arginine decreases insulin level and improves insulin sensitivity; TNF-alpha plays role in the pathogenesis of insulin resistance in patients with obesity | |
| Jabłecka et al. (2012) [71] | 2 months | 3 × 2 g/day orally | + | 12–38 | L-arginine does not affect fasting glucose and HbA1 level in diabetic patients with atherosclerotic peripheral arterial disease, but increases NO and TAS levels | |
| Bogdanski et al. (2013) [72] | 6 months | 3 × 9 g/day orally | + | 44 | L-arginine decreases plasminogen activator type 1, increases NO and TAS levels, and improves insulin sensitivity in obese patients | |
| Suliburska et al. (2014) [73] | 6 months | 3 × 9 g/day orally | + | 44 | L-arginine affects zinc serum concentrations in obese patients; positive correlation between the change in zinc and insulin sensitivity improvement was observed | |
| Monti et al. (2013) [74] | 6 weeks (2 weeks of intervention) | 6.6 g/day orally | cross-over study | 7–8/15 | L-arginine improves glucose metabolism, insulin secretion and insulin sensitivity; it enhances endothelial function in patients with impaired glucose tolerance and metabolic syndrome | |
| Monti et al. (2012) [75] | 18 months + 12-month follow-up period | 6.4 g/day orally | + | 72 | L-arginine improves β-cell function and insulin sensitivity, and increase probability to become normal glucose tolerant, but does not reduce the incidence of diabetes in patients with impaired glucose tolerance and metabolic syndrome | |
| Monti et al. (2018) [76] | 18 months + 90-month follow-up | 6.4 g/day orally | + | 45–47 | L-arginine delays the development of T2DM; the effect could be related to reduction in oxidative stress | |