INSULIN RESISTANCE RESULTING

FROM OBESITY
Megan Walker

Introduction
Obesity is a direct cause of insulin resistance and is a result from

unhealthy eating and/or lack of exercise

Type II diabetes is described by not being able to respond to insulin

Insulin is the primary regulator of carbohydrate, fat, and protein

metabolism
Insulin is a hormone that regulates blood glucose levels and regulates how the body

uses and stores glucose and fat.

Insulin is a hormone that is produced by the beta cells of the pancreas.
Body's cells need insulin to take glucose from the blood for energy

The underlying cause of insulin resistance appears to be

inflammation that can be increased by the fatty acid composition of

the diet(1)
Insulin resistance involves a defect in one of the mechanisms regulating GLUT4

protein
Free fatty acids

Insulin Resistant Organs

Liver
Large accumulation of FFA
Fatty liver is strongly associated with insulin resistance.
Accumulation of fat in the liver is a manifestation of the disordered
control of lipids that occurs with insulin resistance.
Skeletal muscle
Insulin resistance in muscle and fat cells reduces glucose uptake,

whereas insulin resistance in liver cells results in reduced glycogen

synthesis and storage and also a failure to suppress glucose
production and release into the blood

Adipose tissue
Swelling of fat cells

Panayota Mitrou, et al. horm.2002 , 2013.

The toxic effect of increased levels of non-esterified fatty acids, known

as lipotoxicity gradually impairs insulin action on the liver and muscle,
resulting in insulin resistance.

Diagram showing insulin resistance in a muscle cell

Coletta D, et al. 2011

High fructose study on rats(5)

This study was to investigate the effects of a long-term high-fructose

diet on the insulin signaling pathway of the hippocampus

Rats were fed either on a control (0% fructose solution) or highfructose diet (10% fructose solution).
Food intake and body mass were measured regularly for eight
months
Compared to the control group, the high fructose group exhibited
more weight gain, peripheral insulin resistance, metabolic disorders,
and memory impairments
These results suggested that a high-fructose diet induced peripheral
insulin resistance and an abnormal insulin signaling pathway in the
hippocampus which exacerbated memory deficits in the rats.

Significance
Obesity is preventable
Insulin resistance resulting from obesity is very prevalent
Among U.S. residents aged 65 years and older, 10.9 million, or

26.9%, had diabetes in 2010. (6) Even children are getting type 2
diabetes as a result from diet and exercise
Dietitians are able to help people overcome type 2 diabetes by
changing their diet and exercise which will lower the prevalence and
people will be all around healthier

Conclusion
The role of fatty acids interactions with specific binding sites in

different organs are related to the wide range of the adverse

metabolic consequences associated with insulin resistance. It
appears that insulin resistance starts in the hypothalamus causing a
disruption in the balance of satiety and hunger signals. This leads to
overconsumption of calories. Although excess calories and fat can be
stored safely in the adipose tissue, as the inflammation increases in
this organ and insulin resistance develops in the fat cells, the ability to
safely store excess fat is compromised. One of the consequences of
insulin resistance in the adipose tissue is that excess fat is released
into the blood stream and is repossessed by other organs (liver and
skeletal muscles) that are not equipped to safely store this excess fat.
This is the start of lipotoxicity.

References
1. Sears B, Perry M. The role of fatty acids in insulin resistance. Lipids Health Dis.

2015;14.
2. Mitrou P, Raptis S, Dimitriadis G. Insulin action in morbid obesity: a focus on muscle
and adipose tissue. HJ. 2013;12(2):201-213.
3. Coletta D, Mandarino L. Mitochondrial dysfunction and insulin resistance from the
outside in: extracellular matrix, the cytoskeleton, and mitochondria. AJP: Endocrinology
and Metabolism. 2011;301(5):E749-E755.
4. Byun A, Lee S, Lee H, Shim K. What is the most appropriate lipid profile ratio
predictor for insulin resistance in each sex? A cross-sectional study in Korean
populations (The Fifth Korea National Health and Nutrition Examination Survey).
Diabetol Metab Syndr. 2015.
5. Wu H, Ren L, Zhou X, Han D. A high-fructose diet induces hippocampal insulin
resistance and exacerbates memory deficits in male Sprague-Dawley rats. Nutritional
Neuroscience. 2015;18(7):323-328.
6. CDC. National Diabetics. 2015. Available at:
http://www.cdc.gov/diabetes/pubs/factsheet11.htm. Accessed November 25, 2015.