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Published on: February 7, 2011
Amino acid transport in diaphragms from newborn rats: evidence for insulin resistance
Insights
Young rats exhibit insulin resistance due to high circulating insulin levels, impacting amino acid transport in muscle tissue. This study reveals how early-life insulin exposure affects glucose and amino acid metabolism.
Area of Science:
- Endocrinology
- Molecular Biology
- Physiology
Background:
- Insulin is a key regulator of glucose and amino acid transport in mammalian tissues.
- Insulin sensitivity can be modulated by various factors, including age and hormonal environment.
- The transport of alpha-aminoisobutyrate (AIB) is a well-established model for studying insulin's effects on amino acid uptake.
Purpose of the Study:
- To investigate the age-dependent insulin sensitivity of amino acid transport in rat diaphragms.
- To determine the underlying mechanisms of altered insulin sensitivity in young versus adult rats.
- To explore the role of endogenous insulin levels in mediating insulin resistance.
Main Methods:
- In vitro insulin stimulation assays on rat diaphragm tissues from rats of varying ages (1 day to 5 weeks).
- Measurement of alpha-aminoisobutyrate (AIB) uptake kinetics (Km and Vmax).
- Analysis of plasma insulin levels in donor rats at different ages and after experimental manipulation.
Main Results:
- Diaphragms from 1-day-old rats showed minimal response to insulin for AIB transport, unlike older tissues.
- AIB uptake was higher in 1-day-old diaphragms, attributed to decreased Km and elevated Vmax.
- Insulin resistance in young rats correlated with significantly higher endogenous plasma insulin levels.
- Experimental elevation of plasma insulin in older rats induced insulin resistance in vitro.
Conclusions:
- Neonatal exposure to high insulin levels induces insulin resistance in rat diaphragms.
- The A system for amino acid transport remains intact, suggesting the resistance is post-receptor.
- Early-life hyperinsulinemia is a critical factor in the development of insulin resistance, impacting amino acid metabolism.
Abstract:
Diaphragms from rats under 24-h-old did not show the well-known increased transport of alpha-aminoisobutyrate found in older tissues in respone to insulin in vitro. A small effect was apparent by 3 days, and stimulation increased as donor rats aged (up to 4--5 wk). One-day diaphragms also had greater uptake than older tissues, due to both decreased Km and elevated Vmax. The change in insulin sensitivity did not result from alteration in the transport system used by alpha-aminoisobutyrate because uptake showed characteristics of the A system at both 1 day and older. Results suggest instead that the 1-day tissues had been made insulin-resistant by high insulin levels in donor animals. Plasma insulin levels of 1-day-old rats were 5 times those of 5-day animals. Elevating the plasma insulin levels of 5-day or 25- to 35-day rats led to a decreased effectiveness of insulin in vitro in stimulating alpha-aminoisobutyrate transport into their diaphragms. In the older animals, the stimulation was inversely proportional to the plasma insulin level 2 h after insulin injection.
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