*3.3. Antidiabetic E*ff*ect*

Type 2 diabetes, accounting for 90–95% of all diabetes cases, is a severe health problem affecting over 380 million people worldwide [106]. Elevated blood glucose levels, insulin resistance, and low insulin sensitivity are the main characteristics of patients with type 2 diabetes [107], resulting in serious conditions, including arteriosclerosis, renal damage, and retinopathy [108]. In a streptozotocin-induced animal model of diabetes, several studies have been conducted to elucidate the mechanisms underlying the antidiabetic activity of *Chlorella* supplementation [109–111]. Shibata et al. [109] evaluated the effects of *Chlorella* supplementation on antioxidant status and cataracts by feeding a diet containing 7.3% (*w*/*w*) *Chlorella* powder (*C*. *regularis*) to 11-week old rats with streptozotocin-induced diabetes. After 11 weeks of supplementation, serum lipid peroxide levels (an index of oxidative status) and blood glycated hemoglobin were lower in *Chlorella*-supplemented rats than in control rats; however, the serum glucose level did not differ between groups. *Chlorella* supplementation delayed the development of lens opacities. These results indicate that *Chlorella* supplementation might be beneficial for preventing diabetes complications such as cataracts, possibly due to the activity of its antioxidant compounds.

Cherng and Shih reported potential hypoglycemic effects of *Chlorella* supplementation in streptozotocin-induced diabetic mice [110]. Oral administration of *Chlorella* 60 min before glucose administration (0.5 g/kg body weight) resulted in a transient hypoglycemic effect at 90 min after glucose administration without an increase in insulin secretion. *Chlorella* supplementation increased 2-deoxyglucose uptake in the liver and soleus muscles of streptozotocin-treated mice and was likely the cause of the observed hypoglycemic effects [111].

The prophylactic effect of *Chlorella* (*C. vulgaris*) supplementation on diabetes was studied by Vecina et al. [112], who investigated body weight, lipid profile, blood glucose, and insulin signaling in liver, skeletal muscle, and adipose tissue in high-fat diet-induced obese mice. *Chlorella* supplementation improves glycemic control in obesity and diabetes because it decreases insulin resistance caused by increased expression of glucose transporter 4 via the activation of protein kinase B phosphorylation in skeletal muscle. *Chlorella* supplementation combined with aerobic exercise training showed more pronounced effects on the improvement of glycemic control via increased activation of muscle phosphorylation signaling in type 2-diabetic rats [113].

A randomized, double-blind, placebo-controlled human study was conducted in 28 borderline-diabetic participants treated with either *Chlorella* (8 g/day) or placebo for 12 weeks [114]. The expression levels of 252 genes, including six associated with type 2 diabetes, differed between the two groups. Notably, the mRNA expression level of resistin, an insulin resistance inducer, was significantly lower in the *Chlorella* group than in the placebo group and correlated with the expression levels of hemoglobin A1c, tumor necrosis factor-a, and interleukin-6 [114], all of which are involved in glucose metabolism and/or inflammation.
