What does this research mean for the field?

ANGPTL8 improves glucose tolerance in gestational diabetes mellitus (GDM) mice and enhances glucose uptake in insulin-resistant HepG2 cells via the PI3K/Akt pathway. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

February 26, 2026BMC Pregnancy and ChildbirthOpen Access

ANGPTL8 regulates glucose metabolism in gestational diabetes mellitus mice, and proteomic analysis reveals the PI3K/Akt pathway plays its role in insulin-resistance HepG2 cells

Q: What is the clinical evidence from this study?

Study design: Other. Population: gestational diabetes mellitus (n=20). Intervention: ANGPTL8 over-expression via hydrodynamic tail vein injection vs. control virus (Scramble AAV-8). Primary outcome: glucose tolerance measured by oral glucose tolerance test (OGTT) at gestational day 8.5.

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Key result

ANGPTL8 over-expression improves glucose tolerance versus controls in GDM mice.

n=20

Why the study?

The functions of ANGPTL8 in the metabolic profiles of insulin-resistant HepG2 cells, glucose tolerance in GDM mice, and the underlying mechanisms required further exploration.

Does ANGPTL8 over-expression improve glucose tolerance and insulin resistance in GDM mice and HepG2 cells?

Population

Insulin-resistant HepG2 cell lines and a pregnant mouse model of GDM

Comparison

ANGPTL8 over-expression vs knockout vs wild-type in cells, and ANGPTL8 over-expressing vs control GDM mice

Design

In vitro and in vivo preclinical animal and cell study

Authors

XZXiu ZhengAerospace Center Hospital JYJianying YanFujian Medical University XCXiaoyun ChenFujian Medical University

Discussion

Member takes

Implication

Should not change GDM practice; leaves open ANGPTL8 modulation as hypothesis-generating for human insulin resistance.

Key Points

To examine the effects of ANGPTL8 on insulin resistance in HepG2 cells and glucose tolerance in gestational diabetes mellitus (GDM) mouse models, and to elucidate the underlying signaling pathways.
Generated ANGPTL8 knockout and over-expressing HepG2 cell lines to evaluate glucose uptake and downstream proteomic and metabolomic alterations under high-insulin conditions.
Established a GDM model in pregnant C57BL/6J mice using a high-fat diet combined with intraperitoneal streptozotocin injections.
Conducted oral glucose tolerance tests and evaluated Akt activation in primary hepatocytes from GDM mice transfected with m-ANGPTL8 versus untransfected controls.
HepG2 cells over-expressing ANGPTL8 exhibited a marked enhancement in glucose uptake under insulin-resistant conditions compared with wild-type and knockout lines, along with substantial down-regulation of lactate and branched-chain amino acids.
GDM mice transfected with m-ANGPTL8 displayed significantly better glucose tolerance on oral glucose tolerance tests than untransfected GDM mice.
ANGPTL8 translation was elevated in liver, pancreas, and placental tissues of GDM mice, promoting Akt activation via the PI3K/Akt/GSK-3β pathway.

Structured PICO

Does ANGPTL8 over-expression improve glucose tolerance and insulin resistance in GDM mice and HepG2 cells?

Population

Healthy 6-weeks-old C57BL/6J female mice (n=20) and HepG2 cell lines (wild-type, ANGPTL8 knockout, and over-expressing).

Intervention

ANGPTL8 over-expression (pAAV8-m-ANGPTL8-Flag at 2x10^13 genome copy/kg via hydrodynamic tail vein injection in mice; viral transduction in HepG2 cells).

Comparator

Scramble AAV-8 injection in GDM mice; wild-type and ANGPTL8 knockout HepG2 cells.

Outcome

Glucose uptake capacity in HepG2 cells and glucose tolerance via oral glucose tolerance test (OGTT) in GDM mice.surrogate

ANGPTL8 over-expression enhances glucose uptake and improves glucose tolerance in gestational diabetes models via the PI3K/Akt/GSK-3β pathway.

Limitations

Small sample size for animal study (n=4 per group in intervention)
Lack of explicit quantitative data reported for primary endpoint in manuscript
Animal study results may not fully translate to humans

Cite This Study

Zheng et al. (2026) studied gestational diabetes mellitus (n=20). ANGPTL8 over-expression via hydrodynamic tail vein injection vs. control virus (Scramble AAV-8) was evaluated on glucose tolerance measured by oral glucose tolerance test (OGTT) at gestational day 8.5. ANGPTL8 over-expression improved glucose tolerance in gestational diabetes mellitus mice compared to controls, as evidenced by improved OGTT profiles.

synapsesocial.com/papers/699fe37b95ddcd3a253e7539 https://doi.org/10.1186/s12884-026-08738-6

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February 26, 2026BMC Pregnancy and ChildbirthOpen Access

ANGPTL8 regulates glucose metabolism in gestational diabetes mellitus mice, and proteomic analysis reveals the PI3K/Akt pathway plays its role in insulin-resistance HepG2 cells

View Full Paper

Ask AI

Bookmark

Key result

ANGPTL8 over-expression improves glucose tolerance versus controls in GDM mice.

n=20

Why the study?

The functions of ANGPTL8 in the metabolic profiles of insulin-resistant HepG2 cells, glucose tolerance in GDM mice, and the underlying mechanisms required further exploration.

Does ANGPTL8 over-expression improve glucose tolerance and insulin resistance in GDM mice and HepG2 cells?

Population

Insulin-resistant HepG2 cell lines and a pregnant mouse model of GDM

Comparison

ANGPTL8 over-expression vs knockout vs wild-type in cells, and ANGPTL8 over-expressing vs control GDM mice

Design

In vitro and in vivo preclinical animal and cell study

Authors

XZXiu ZhengAerospace Center Hospital JYJianying YanFujian Medical University XCXiaoyun ChenFujian Medical University

Discussion

Member takes

Implication

Should not change GDM practice; leaves open ANGPTL8 modulation as hypothesis-generating for human insulin resistance.

Key Points

To examine the effects of ANGPTL8 on insulin resistance in HepG2 cells and glucose tolerance in gestational diabetes mellitus (GDM) mouse models, and to elucidate the underlying signaling pathways.
Generated ANGPTL8 knockout and over-expressing HepG2 cell lines to evaluate glucose uptake and downstream proteomic and metabolomic alterations under high-insulin conditions.
Established a GDM model in pregnant C57BL/6J mice using a high-fat diet combined with intraperitoneal streptozotocin injections.
Conducted oral glucose tolerance tests and evaluated Akt activation in primary hepatocytes from GDM mice transfected with m-ANGPTL8 versus untransfected controls.
HepG2 cells over-expressing ANGPTL8 exhibited a marked enhancement in glucose uptake under insulin-resistant conditions compared with wild-type and knockout lines, along with substantial down-regulation of lactate and branched-chain amino acids.
GDM mice transfected with m-ANGPTL8 displayed significantly better glucose tolerance on oral glucose tolerance tests than untransfected GDM mice.
ANGPTL8 translation was elevated in liver, pancreas, and placental tissues of GDM mice, promoting Akt activation via the PI3K/Akt/GSK-3β pathway.

Structured PICO

Does ANGPTL8 over-expression improve glucose tolerance and insulin resistance in GDM mice and HepG2 cells?

Population

Healthy 6-weeks-old C57BL/6J female mice (n=20) and HepG2 cell lines (wild-type, ANGPTL8 knockout, and over-expressing).

Intervention

ANGPTL8 over-expression (pAAV8-m-ANGPTL8-Flag at 2x10^13 genome copy/kg via hydrodynamic tail vein injection in mice; viral transduction in HepG2 cells).

Comparator

Scramble AAV-8 injection in GDM mice; wild-type and ANGPTL8 knockout HepG2 cells.

Outcome

Glucose uptake capacity in HepG2 cells and glucose tolerance via oral glucose tolerance test (OGTT) in GDM mice.surrogate

ANGPTL8 over-expression enhances glucose uptake and improves glucose tolerance in gestational diabetes models via the PI3K/Akt/GSK-3β pathway.

Limitations

Small sample size for animal study (n=4 per group in intervention)
Lack of explicit quantitative data reported for primary endpoint in manuscript
Animal study results may not fully translate to humans

Cite This Study

synapsesocial.com/papers/699fe37b95ddcd3a253e7539 https://doi.org/10.1186/s12884-026-08738-6

Also Consider

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