Table 2.

Experimental studies on the effects of GABA and EVs in diabetes mellitus.

Compound	Source/Origin	Model System	Main Findings	Study
GABA	GABA-containing fermented mung bean extract with Mardi rhizopus 5351 inoculums, low and high doses	T1D Balb/c induced T1D with high doses of alloxan (100 mg/kg BW) and glucose-induced hyperglycaemic Balb/c mice	Glucose-induced mice: ↓FBG Alloxan-induced mice: ↓ Reduced FBG, ↑insulin serum levels, ↓ TC and TG serum levels (vs. nonfermented), restored antioxidant status (↓MDA and NO)	Yeap et al., 2012 [84]
	Yogurt fermented with Streptococcus thermophiles fmb5, low and high doses	C57BL/6 mice induced T2D with low doses of STZ (100 mg/kg BW)	Low and high doses: No hypoglycaemic effect, ↑HOMA-β, improved glucose tolerance and insulin resistance, normalised fat, kidney and liver coefficients, ↓serum urea nitrogen, no effect on HbA1c nor BW. High doses: Normalised pancreatic histology, preserved islet cells function, ↓ TC and LDL, HDL	Li et al., 2020 [95]
EVs	Akkermansia muciniphila ATCC BAA-835	C57BL/6 mice induced T2D with HFD	In vivo: Reduced BW, attenuated intestinal damage following HFD, increase expression of tight junction proteins, improved glucose tolerance (OGTT) In vitro: Enhanced barrier function in Caco-2 cells	Chelakkot et al., 2018 [40]

AUC: area under the curve; BW: body weight; EVs: extracellular vesicles; FBG: fasting blood glucose; GABA: γ-aminobutyric acid; GIP: gastric inhibitory polypeptide; GLP-1: glucagon-like peptide-1; GM: gut microbiota; HFD: high fat diet; HOMA: homeostasis model assessment-β; LDL: low-density lipoprotein; MDA: malondiadehyde; NO: nitric oxide; OGTT: oral glucose tolerance test; PYY: peptide YY; STZ: streptozotocin; TC: total cholesterol; TG: triglyceride; T1D: type 1 diabetes; T2D: type 2 diabetes. ↑ means increase, ↓ means decrease.