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Updated: Jun 17, 2025
Analysis of Non-Human Primate Pancreatic Islet Oxygen Consumption
Published on: December 18, 2019
Analysis of beta-cell maturity and mitochondrial morphology in juvenile non-human primates exposed to maternal
Darian T Carroll1, Allie Miller2, Jennifer Fuhr2,3
1Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, United States.
Insights
Maternal Western-style diet (mWSD) did not alter beta-cell maturity or mitochondrial structure in offspring. However, increased NKX6.1 expression was observed in 3-year-old offspring, suggesting potential long-term effects on beta-cell function.
Area of Science:
- Endocrinology
- Developmental Biology
- Mitochondrial Biology
Background:
- Maternal Western-style diet (mWSD) impacts offspring islet development and insulin secretion.
- Mitochondria are crucial for beta-cell function and adapt to nutrient stress.
- Mitochondrial dynamics influence cellular fate, prompting investigation into beta-cell maturity and morphology.
Purpose of the Study:
- To assess if mWSD exposure alters beta-cell maturity markers in offspring.
- To investigate changes in beta-cell mitochondrial morphology due to maternal WSD.
- To determine if these factors explain previously observed offspring islet phenotypes.
Main Methods:
- Evaluated beta-cell maturity markers (NKX6.1, MAFB, UCN3) using fluorescence microscopy in Japanese macaque offspring.
- Analyzed mitochondrial morphology in beta cells via transmission electron microscopy (2D) and super-resolution microscopy (3D).
- Assessed offspring at pre-adolescent (1 year) and peri-adolescent (3 years) stages.
Main Results:
- No significant difference in beta-cell maturity marker expression at 1 or 3 years, except for increased NKX6.1 in 3-year-old WSD-exposed offspring.
- Beta-cell mitochondrial networks were predominantly short and fragmented in all NHP offspring, increasing in volume with age.
- Maternal WSD exposure may contribute to increased mitochondrial fragmentation during development.
Conclusions:
- Maternal WSD does not appear to affect offspring beta-cell maturity or mitochondrial network morphology.
- Observed developmental effects on islet cell ratio and insulin secretion are not mediated by these factors.
- A fragmented mitochondrial network may confer greater metabolic flexibility in NHP beta cells.
Introduction:
Using a non-human primate (NHP) model of maternal Western-style diet (mWSD) feeding during pregnancy and lactation, we previously reported altered offspring beta:alpha cell ratio in vivo and insulin hyper-secretion ex vivo. Mitochondria are known to maintain beta-cell function by producing ATP for insulin secretion. In response to nutrient stress, the mitochondrial network within beta cells undergoes morphological changes to maintain respiration and metabolic adaptability. Given that mitochondrial dynamics have also been associated with cellular fate transitions, we assessed whether mWSD exposure was associated with changes in markers of beta-cell maturity and/or mitochondrial morphology that might explain the offspring islet phenotype.
Methods:
We evaluated the expression of beta-cell identity/maturity markers (NKX6.1, MAFB, UCN3) via florescence microscopy in islets of Japanese macaque pre-adolescent (1 year old) and peri-adolescent (3-year-old) offspring born to dams fed either a control diet or WSD during pregnancy and lactation and weaned onto WSD. Mitochondrial morphology in NHP offspring beta cells was analyzed in 2D by transmission electron microscopy and in 3D using super resolution microscopy to deconvolve the beta-cell mitochondrial network.
Results:
There was no difference in the percent of beta cells expressing key maturity markers in NHP offspring from WSD-fed dams at 1 or 3 years of age; however, beta cells of WSD-exposed 3 year old offspring showed increased levels of NKX6.1 per beta cell at 3 years of age. Regardless of maternal diet, the beta-cell mitochondrial network was found to be primarily short and fragmented at both ages in NHP; overall mitochondrial volume increased with age. In utero and lactational exposure to maternal WSD consumption may increase mitochondrial fragmentation.
Discussion:
Despite mWSD consumption having clear developmental effects on offspring beta:alpha cell ratio and insulin secretory response to glucose, this does not appear to be mediated by changes to beta-cell maturity or the beta-cell mitochondrial network. In general, the more fragmented mitochondrial network in NHP beta cells suggests greater ability for metabolic flexibility.
