Metabolic Regulation of Glucose and Lipid Homeostasis

The coordinated regulation of glucose and lipid homeostasis is fundamental to energy balance and overall health. Central to this regulation are hormonal signals—principally insulin and glucagon—that modulate nutrient uptake, storage and utilisation across key organs including liver, skeletal muscle and adipose tissue. In the fed state, insulin promotes glucose uptake into muscle and adipose depots while simultaneously inhibiting hepatic glucose production; it also stimulates lipogenesis and suppresses lipolysis. During fasting, glucagon stimulates hepatic gluconeogenesis and lipid mobilisation from adipose stores to preserve circulating fuel. Cross-talk between tissues is mediated by adipokines, myokines and hepatokines, creating feedback loops that fine-tune metabolic flux. Dysregulation of these processes underlies common disorders such as type 2 diabetes, non-alcoholic fatty liver disease and obesity. Advances in molecular biology have illuminated signalling cascades—PI3K–AKT, AMPK and mTOR among others—that integrate nutrient sensing with transcriptional control, while systems approaches reveal the impact of genetic, epigenetic and environmental factors. Understanding these interconnections is vital for developing targeted interventions to restore metabolic equilibrium and mitigate cardiometabolic disease risk.

Research from Nature Portfolio

Recent methodological advances have standardised the computation of muscle-specific insulin sensitivity indices derived from oral glucose tolerance test data, yielding improved agreement with clamp-based measures and enabling more consistent assessment across diverse sampling protocols. Concurrently, refined imaging analyses of visceral adipose tissue have characterised distinct inflammatory and glucose uptake signatures, uncovering potential biomarkers of adipose dysfunction that reflect systemic metabolic and inflammatory status beyond traditional anthropometrics.

Metabolic Regulation of Glucose and Lipid Homeostasis publication trend

The graph below shows the total number of articles in metabolic regulation of glucose and lipid homeostasis across all publications each year (not limited to Nature Index journals).

Technical terms

Insulin resistance: A condition in which target tissues (muscle, liver, adipose) respond poorly to circulating insulin, impairing glucose uptake and promoting hyperglycaemia.

Insulin sensitivity: The capacity of cells to respond to insulin’s actions, inversely related to insulin resistance and critical for maintaining normoglycaemia.

Homeostasis: The dynamic equilibrium by which physiological systems maintain stable internal conditions despite external fluctuations.

Adipose tissue: A specialised connective tissue that stores energy as lipid, secretes hormones and cytokines, and participates in thermal insulation and mechanical protection.

Metabolic phenotype: The composite profile of an individual’s tissue-specific metabolic characteristics—such as hepatic or muscle insulin resistance—that influences response to interventions.

References

1. Improved quantification of muscle insulin sensitivity using oral glucose tolerance test data: the MISI Calculator. Scientific Reports (2019).
2. Characterization of glucose uptake metabolism in visceral fat by 18 F-FDG PET/CT reflects inflammatory status in metabolic syndrome. PLOS ONE (2020).
3. Cardiometabolic health improvements upon dietary intervention are driven by tissue-specific insulin resistance phenotype: A precision nutrition trial. Cell Metabolism (2023).
4. HDAC5 controls a hypothalamic STAT5b-TH axis, the sympathetic activation of ATP-consuming futile cycles and adult-onset obesity in male mice. Molecular Metabolism (2024).
5. Association between Visceral Adipose Tissue Metabolism and Cerebral Glucose Metabolism in Patients with Cognitive Impairment. International Journal of Molecular Sciences (2024).