# ANABOLIC ACTIONS OF INSULIN IN NEUROMUSCULAR DISEASE

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 1991 · $225,557

## Abstract

The studies in this application focus upon the most common form of
muscular dystrophy, myotonic dystrophy.  This autosomal dominant
disorder is felt to be due to an inherited defect in the cell
membrane.  The patients have marked resistance to insulin
stimulation of glucose uptake by forearm muscles.  This insulin
resistance may results from the putative membrane defect which has
compromised the function of the insulin receptor.  The present
proposal will test the following hypothesis: Muscle wasting in
myotonic dystrophy results form a hereditary defect that has not
only decreased the action of insulin in stimulating muscle glucose
uptake, but has also damaged the ability of insulin to slow the
rate of muscle breakdown and its ability to increase muscle protein
synthesis.

To test this hypothesis patients with myotonic dystrophy,
comparably wasted patients with other neuromuscular diseases, and
normals will be studied.  The investigations will use the human
forearm technique in combination with a three hour euglycemic
insulin infusion to examine insulin-mediated retention of amino
acids and insulin stimulation of glucose and potassium uptake. The
four different rates of insulin infusion used (20, 30, 40, and 80
mU/m2/min) will achieve steady-state elevations of insulin in the
low, middle and high physiologic ranges, infusion of the stable
isotope, L-(ring 2H5)-phenylalanine during the glucose clamp
procedures will allow measurement of the effectiveness of insulin
in controlling the rate of skeletal muscle breakdown, in
stimulating amino acid uptake, and in promoting protein synthesis.

The net balance of 3-methylhistidine across forearm muscle will be
determined before and during each of the insulin infusions.  The
release of 3-methylhistidine by muscle will provide another measure
of the insulin infusions.  The release of 3-methylhistidine by
muscle will provide another measure of the anticatabolic action of
insulin on protein degradation in patients with myotonic dystrophy.
These findings will complement the results obtained with the 2H5
phenylalanine infusion.

The investigations will define more clearly the relationship
between the insulin resistance and muscle wasting that occurs in
myotonic dystrophy.  The findings will clarify whether the muscle
wasting is associated with a decrease in the ability of insulin to
regulate muscle protein breakdown or with a decrease in the ability
of insulin to stimulate protein synthesis or both.  This formation
will help to promote the development of new therapeutic strategies
and might also lead to new approaches in the treatment of other
insulin resistant states, such as, diabetes and obesity.  The
present investigations will also provide additional new, diabetes
and obesity. The present investigations will also provide
additional new information about the actions of insulin on the
regulation of protein metabolism in normal man.

## Key facts

- **NIH application ID:** 3158894
- **Project number:** 5R01AR038894-03
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **SAM.gov UEI:** F27KDXZMF9Y8
- **Principal Investigator:** RICHARD T MOXLEY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $225,557
- **Award type:** 5
- **Project period:** 1989-03-01 → 1993-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3158894

## Citation

> US National Institutes of Health, RePORTER application 3158894, ANABOLIC ACTIONS OF INSULIN IN NEUROMUSCULAR DISEASE (5R01AR038894-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3158894. Licensed CC0.

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