ArticleDiabetologia2015
Suppression of hyperinsulinaemia in growing female mice provides long-term protection against obesity.
Article in Diabetologia, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 100 citations in OpenAlex.
- The effects of purslane consumption on blood pressure, body weight, body mass index, and waist circumference: a systematic review and meta-analysis of randomised controlled.Journal of nutritional science · 2023Pooled it
- Nutrient and non-nutrient regulators of insulin secretion.Nature reviews. Endocrinology · 2026Review
- Extracellular 70 kDa heat shock protein in blood plasma binds insulin and modulates glycaemic control in vivo.Cell stress & chaperones · 2026Article
- Hyperinsulinaemia as a cause of obesity and cardiometabolic diseases.Nature reviews. Endocrinology · 2026Review
- Beta-cell-specific C3 deficiency exacerbates metabolic dysregulation and insulin resistance in obesity.Molecular metabolism · 2026Article
- Placental mitochondrial calcium uniporter modulates offspring susceptibility to metabolic dysfunction.Molecular metabolism · 2025Article
- Characterizing the effects of Dechlorane Plus on β-cells: a comparative study across models and species.Islets · 2024Article
- Alterations in Adipose Tissue Distribution, Cell Morphology, and Function Mark Primary Insulin Hypersecretion in Youth With Obesity.Diabetes · 2024Article
- Article
- Obesity Duration and Cardiometabolic Disease.Arteriosclerosis, thrombosis, and vascular biology · 2023Review
- Metformin reduces insulin resistance and attenuates progressive renal injury in prepubertal obese Dahl salt-sensitive rats.American journal of physiology. Renal physiology · 2023Article
- Hyperinsulinemia Influences the Short-Term Efficiency of Laparoscopic Sleeve Gastrectomy for Patients with Obesity and Insulin Resistance.Diabetes, metabolic syndrome and obesity : targets and therapy · 2023Article
- Lack of Evidence for a Causal Role of Hyperinsulinemia in the Progression of Obesity in Children and Adolescents: A Longitudinal Study.Diabetes care · 2022Article
- Article
- Direct anabolic metabolism of three-carbon propionate to a six-carbon metabolite occurs in vivo across tissues and species.Journal of lipid research · 2022Article
- Effects of hyperinsulinemia on pancreatic cancer development and the immune microenvironment revealed through single-cell transcriptomics.Cancer & metabolism · 2022Article
- Beta-cell specific Insr deletion promotes insulin hypersecretion and improves glucose tolerance prior to global insulin resistance.Nature communications · 2022Article
- Central Nervous System Control of Glucose Homeostasis: A Therapeutic Target for Type 2 Diabetes?Annual review of pharmacology and toxicology · 2022Review
- On the causal relationships between hyperinsulinaemia, insulin resistance, obesity and dysglycaemia in type 2 diabetes.Diabetologia · 2021Article
- Therapeutic opportunities for pancreatic β-cell ER stress in diabetes mellitus.Nature reviews. Endocrinology · 2021Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
aims/hypothesisHyperinsulinaemia is associated with obesity but its causal role in the onset of obesity remains controversial. In this study, we tested the hypothesis that transient attenuation of diet-induced insulin hypersecretion in young mice can provide sustained protection against obesity throughout adult life.
methodsUsing 'genetically humanised' mice lacking both alleles of rodent-specific Ins1, we compared mice heterozygous for the ancestral insulin gene Ins2 with Ins2(+/+) controls. Female Ins1(-/-):Ins2(+/-) and Ins1(-/-):Ins2(+/+) littermates were fed chow or high-fat diet (HFD). Insulin secretion, metabolic health variables and body mass/composition were tracked for over 1 year. We examined islet function and adipose transcript levels of adipogenic, lipogenic and lipolytic genes at two time points.
resultsIn control Ins1(-/-):Ins2(+/+) mice, HFD resulted in elevated fasting and glucose-stimulated insulin secretion between 8 weeks and 27 weeks of age. Hyperinsulinaemia was reduced by nearly 50% in Ins1(-/-):Ins2(+/-) mice during this period, without lasting adverse effects on glucose homeostasis. This corresponded with attenuated weight gain and adiposity. White adipose tissue from Ins1(-/-):Ins2(+/-) mice had fewer large lipid droplets, although transcriptional changes were not detected. Importantly, Ins1(-/-):Ins2(+/-) mice remained lighter than Ins1(-/-):Ins2(+/+) littermates despite reaching an equivalent degree of hyperinsulinaemia on HFD by 52 weeks. CONCLUSIONS/
interpretationThese data demonstrate that attenuation of hyperinsulinaemia in young, growing female mice provides a long-lasting protection against obesity. This protection persists despite a late-onset emergence of hyperinsulinaemia in HFD-fed Ins1(-/-):Ins2(+/-) mice. Given the evolutionary conserved roles of insulin, it is possible that suppressing hyperinsulinaemia early in life may have far-reaching consequences on obesity in full-grown adult humans.
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