Publikasjoner
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Suntharalingam, Anita; Sharma, Archana; Qvigstad, Elisabeth; Sattar, Naveed; Gill, Jason M. R. & Bjørnvall, Christina Dybdrodt
[Vis alle 12 forfattere av denne artikkelen]
(2025).
Differences in tissue-specific insulin resistance between South Asian and Nordic women with prediabetes after gestational diabetes.
Diabetologia.
ISSN 0012-186X.
68(12),
s. 2696–2708.
doi:
10.1007/s00125-025-06546-9.
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Aims/hypothesis
The aim of this work was to investigate tissue-specific insulin resistance in South Asian and Nordic women with previous gestational diabetes mellitus (pGDM) and to evaluate potential ethnic differences contributing to type 2 diabetes risk.
Methods
A cross-sectional study using a two-step hyperinsulinaemic–euglycaemic clamp with a glucose tracer was conducted to assess insulin sensitivity in muscle, liver and adipose tissue in 19 South Asian and 16 Nordic women with pGDM and prediabetes (impaired glucose tolerance and/or impaired fasting glucose), along with 16 ethnicity-specific control women. We assessed inflammation and mitochondrial genes by mRNA sequencing of adipose tissue.
Results
Both South Asian and Nordic women with pGDM showed reduced total glucose disposal (mainly due to muscle insulin resistance) and hyperinsulinaemia compared with the control group. Endogenous glucose production (mainly due to hepatic insulin resistance) was elevated in Nordics with pGDM, while South Asians with pGDM showed pronounced adipose tissue insulin resistance (reduced suppression of glycerol during clamp). mRNA sequencing of adipose tissue indicated increased tissue inflammation in South Asian women compared with Nordic women with pGDM. Furthermore, we observed a differential response to hyperinsulinaemia in South Asians vs Nordics related to mitochondrial mRNA, such as thymidine kinase 2 (TK2). Correlations between adiposity markers and insulin sensitivity also differed by ethnicity, suggesting that the pathways leading to type 2 diabetes may vary across populations.
Conclusions/interpretation
South Asian and Nordic women with pGDM exhibited differences in insulin resistance profiles, with South Asians showing greater adipose tissue insulin resistance and inflammation.
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Dankel, Simon Nitter; Kalleklev, Tine-Lise; Lunde, Siri; Stafsnes, Marit Hallvardsdotter; Bruheim, Per & Aloysius, Thomas Aquinas
[Vis alle 13 forfattere av denne artikkelen]
(2023).
Changes in Plasma Pyruvate and TCA Cycle Metabolites upon
Increased Hepatic Fatty Acid Oxidation and Ketogenesis in
Male Wistar Rats.
International Journal of Molecular Sciences.
ISSN 1661-6596.
24(21).
doi:
10.3390/ijms242115536.
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Altered hepatic mitochondrial fatty acid β-oxidation and associated tricarboxylic acid (TCA) cycle activity contributes to lifestyle-related diseases, and circulating biomarkers reflecting these changes could have disease prognostic value. This study aimed to determine hepatic and systemic changes in TCA-cycle-related metabolites upon the selective pharmacologic enhancement of mitochondrial fatty acid β-oxidation in the liver, and to elucidate the mechanisms and potential markers of hepatic mitochondrial activity. Male Wistar rats were treated with 3-thia fatty acids (e.g., tetradecylthioacetic acid (TTA)), which target mitochondrial biogenesis, mitochondrial fatty acid β-oxidation, and ketogenesis predominantly in the liver. Hepatic and plasma concentrations of TCA cycle intermediates and anaplerotic substrates (LC-MS/MS), plasma ketones (colorimetric assay), and acylcarnitines (HPLC-MS/MS), along with associated TCA-cycle-related gene expression (qPCR) and enzyme activities, were determined. TTA-induced hepatic fatty acid β-oxidation resulted in an increased ratio of plasma ketone bodies/nonesterified fatty acid (NEFA), lower plasma malonyl-CoA levels, and a higher ratio of plasma acetylcarnitine/palmitoylcarnitine (C2/C16). These changes were associated with decreased hepatic and increased plasma pyruvate concentrations, and increased plasma concentrations of succinate, malate, and 2-hydroxyglutarate. Expression of several genes encoding TCA cycle enzymes and the malate–oxoglutarate carrier (Slc25a11), glutamate dehydrogenase (Gdh), and malic enzyme (Mdh1 and Mdh2) were significantly increased. In conclusion, the induction of hepatic mitochondrial fatty acid β-oxidation by 3-thia fatty acids lowered hepatic pyruvate while increasing plasma pyruvate, as well as succinate, malate, and 2-hydroxyglutarate.
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Romuld, Ingunn Bratland; Kalleklev, Tine-Lise; Molnes, Janne; Juliusson, Pétur Benedikt; Njølstad, Pål Rasmus & Sagen, Jørn Vegard
(2021).
Impact of overweight on glucose homeostasis in MODY2 and MODY3.
Diabetic Medicine.
ISSN 0742-3071.
38(10).
doi:
10.1111/dme.14649.
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Publisert
3. sep. 2024 09:27
- Sist endret
25. juli 2025 11:30