Table 3.

Key mechanistic endpoints from animal and in vitro PFAS exposure studies related to glucose and insulin metabolism.

Citation	Experimental Model	PFAS Serum Concentrations or in vitro Exposures	Physiological Endpoints
Yan et al., 2015 (69)	Male Balb/c mice (age 6-8 weeks) were administered PFOA diluted in water for 28 days at the following doses: 0, 0.08, 0.31, 1.25, 5, and 20 mg/kg/d via oral gavage.	Mean Serum PFOA: • 0.08 mg/kg/d – 2.24 ug/mL • 0.31 mg/kg/d – 8 ug/mL • 1.25 mg/kg/d – 25 ug/mL • 5 mg/kg/d – 55 ug/mL • 20 mg/kg/d – 105.3 ug/mL	↑ Increased insulin and glucose sensitivity (GTT and ITT tests). ↑ Increased activation of PI3K-AKT signaling pathway.
Zheng et al., 2017 (70)	Male Balb/c mice (age 6-8 weeks) were administered 1.25 mg/kg/d PFOA for 28 days.	Mean PFOA (± SE): • 55.5 ± 0.50 μg/mL (serum) • 125.9 ± 10.0 μg/g (liver)	↑ Increased fasting blood glucose ↓ Decreased glycogen and glucose content in the liver. No significant change in blood insulin and insulin sensitivity
Qin et al., 2022 (71)	In vivo: C57BL/6 mice administered 1-10 mg/kg/day PFOS via oral gavage for 28 days. In vitro: Mouse β-TC-6 pancreatic cells	Mean Serum PFOS in mice (± SE): • 0 mg/kg/d – 3 ± 2 μmol/L • 1 mg/kg/d – 63 ± 9 μmol/L • 5 mg/kg/d – 234 ± 27 μmol/L • 10 mg/kg/d – 348 ± 47 μmol/Lβ-TC-6 cells: 48-hour exposure to PFOS at 50-100 μmol/L	↓ PFOS exposure in male mice caused reductions of pancreas weight and islet size. ↓ PFOS exposure decreased the insulin release capacity of β-TC-6 cells after glucose stimulation.
Duan et al., 2021(72)	Mouse β-TC-6 pancreatic cells.	β-TC-6 cells: exposure to PFOS at 0-200 µM for 24 or 48 hours.	↓ PFOS exposure (48 h) impaired glucose stimulated insulin secretion. PFOS exposure decreased mitochondrial glucose-induced ATP production and Ca2+ influx.

Down arrow = decreased.

Up arrow = increased.