L-arginine, an endogenous amino acid, is a safe substance that can be found in food. The compound is involved in synthesis of various products responsible for regulatory functions in the body. Particularly noteworthy is, among others, nitric oxide, a signaling molecule regulating carbohydrate and lipid metabolism. The increasing experimental and clinical data indicate that L-arginine supplementation may be helpful in managing disturbed metabolism in obesity, regulate arterial blood pressure or alleviate type 2 diabetes symptoms, but the mechanisms underlying these effects have not been sufficiently elucidated.
Cell Testing | ||||||
Study (Year) | Cell Line/Model | Dose(s) of L-Arginine Tested |
Control Culture | Outcome | ||
Adeghate et al. (2001) [36] | pancreas fragments of diabetic rats |
100 mM | + | L-arginine stimulates insulin secretion | ||
Pi et al. (2012) [37] | 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) [38] | pancreatic islets of Gprc6a−/− mice | 20 mM | + | L-arginine induces insulin secretion, but GPRC6A is not involved in the process | ||
Krause et al. (2011) [39] | 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) [40] | Hep G2 | 1, 3.3, 10 mM | + | L-arginine increase IGF-1 level by stimulating of growth hormone secretion | ||
Cho et al. (2020) [41] | 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) [38] | 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) [40] | 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) [41] | 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) [42] | 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) [43] | 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) [44] | 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) [45] | 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) [46] | 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) [47] | 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) [48] | - | 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) [49] | 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) [50] | 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) [51] | 6 months | 6.4 g/day orally | + | 32 | L-arginine regulates endothelial dysfunction, improves insulin sensitivity and reduces inflammation | |
Bogdański et al. (2012) [52] | 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) [53] | 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) [54] | 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) [55] | 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) [56] | 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) [57] | 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) [58] | 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 |
This entry is adapted from the peer-reviewed paper 10.3390/nu14050961