Assignment 4- Review of Recent Paper

The recent paper I read about Insulin can be found here: http://web.ebscohost.com.qe2a-proxy.mun.ca/ehost/pdfviewer/pdfviewer?hid=18&sid=96135bf0-6f32-4713-a674-482b3822d9f0%40sessionmgr14&vid=2

The title of the paper is : "Diet-induced central obesity and insulin resistance in rabbits".

This study looked at whether a high fat/ high sucrose diet administered to rabbits could result in obesity and insulin resistance. Male japanese white rabbits were dispersed into control and experimental groups. Control rabbits were fed a normal chow diet where as experimental group rabbits were fed the high fat/ high sucrose diet for 36 weeks. Plasma triglycerides, total cholesterol, insulin and glucose levels were measured. Intravenous glucose tolerance tests were also conducted to analyze glucose metabolism. Adipose tissue build up was also compared between the experimental and control rabbits. (Zhao et al. 2008)


The results found no significant difference in triglyceride, total cholesterol, glucose or insulin levels between the two groups over the course of the trial. However, the high fat/high sucrose fed rabbits showed impeded glucose clearance in connection with higher levels of insulin secretion compared to the control rabbits. Control rabbits also had less adipose tissue accumulation than rabbits in the experimental group. These results suggest that the high fat/ high sucrose diet leads to the induction of insulin resistance and weight gain in rabbits.  The study then suggests that rabbits can thus be used as a model for research on human insulin resistance and obesity. (Zhao et al. 2008)


Rabbits do appear to be a better model than rodents for studying insulin resistance in humans as their  lipoprotein profile is more similar. The high fat/ high sucrose diet fed to the rats also resulted in disorders which mimic those found in humans.  The figures presented in the article, such as those labelled figure 1 clearly show the increase glucose and insulin levels in the experimental rabbits compared to the control rabbits during the glucose clearance tests which indicates induced insulin resistance. 

Although the amount of food consumption was no different among the two groups as clearly shown in figure 2, there was a significant increase in body weight of the high fat/ high sucrose fed rabbits. (Zhao et al. 2008)

 As shown in both figures above taken from the study, the claims that a high fat/ high sucrose diet can result in insulin resistance and obesity seem to be supported.  This study was tested on male rabbits, it should be repeated with females to see if the same results will occur. 


To further explore this topic, more long term complications associated with insulin resistance and obesity in rabbits should be measured, for example the progression of heart disease such as arteriosclerosis. It could also be tested if whether these results can be reversed with a return to a healthier diet or treated with exercise. In order to test these treatments, you could take four groups of insulin resistant obese rabbits, subject one to no treatment as a control, treat one with a healthier chow only diet, treat the third group with increased exercise and treat the fourth group with improved diet and an increase in exercise. All groups could be measured for triglyceride level, total cholesterol, glucose and insulin levels as done in this study. Body weight measures and glucose tolerance tests could also be conducted to determine if there are any significant changes to the groups before and after treatments as well as compare the results between groups. It has been suggested that insulin resistance resulting in type 2 diabetes can often be treated or reversed with a switch to a healthier diet and increased exercise. Thus the expected result of these trials would be that all of the treatment groups would have a decrease in insulin resistance and improved overall health compared to the control group. The most significant effects would be expected in the rabbit group treated with both a healthy diet and exercise. 


References:


Zhao, S., Chu, Y., Zhang, C., Lin, Y., Xu, K., Yang, P., et al. (2008). Diet-induced central obesity and insulin resistance in rabbits. Journal of Animal Physiology & Animal Nutrition, 92(1), 105-111. doi:10.1111/j.1439-0396.2007.00723.x.

Assignment 3- Insulin Function and Pathology

Insulin is essential for normal growth and development. It is also the only hormone which functions to lower blood glucose levels. Without it, the body is unable to lower blood glucose levels which results in excess glucose production, ketogenesis, lipolysis, proteolysis and without intervention, ultimately death. An excess of Insulin results in hypoglycemia, which is a lack of blood glucose which can lead to brain failure and death. Thus, Insulin and its functions are extremely important for the body. (Hadley and Levine, 241)


High blood glucose levels trigger the release of Insulin from the pancreatic islets. It then acts on plasmalemmal receptors of a number of different types of cells, most importantly hepatic, muscle and adipose tissue cells. On all of these cells, insulin functions to stimulate the uptake of glucose where it can be metabolized and stored as glycogen or used in the synthesis of proteins or fats.


In fat cells, insulin stimulates glucose uptake which results in increased catabolism of sugar to glycerol. it also activates endothelial cell lipoprotein lipase which triggers the release of FFAs from chylomicrons. the fatty acids are then transported into fat cells where along with glycerol they form triglycerides. These are then added to lipid droplets within adipose cells. this lipid synthesis is stimulated by insulin because it  activates enzymes involved such as citrate lipase, acetyl- CoA carboxylase, fatty acid synthase and glycerol-3-phosphate dehydrogenase.


Insulin also acts on the liver to activate glycogen synthetase which is an enzyme that works to stimulate glycogen formation from glucose. It also indirectly stimulates the conversion of intracellular glucose to glucose-6-PO4 which prevents the release of glucose from hepatocytes.


In muscle cells, insulin prompts the active transport of glucose and amino acids which thus enhances protein synthesis. 


Insulin is also plays a role in potassium homeostasis whereby insulin  stimulates potassium uptake by cells and can result in extracellular hypokalemia (Hadley and Levine 243).


The secretion of insulin is controlled by a number of physiological regulators including endocrine, neural and metabolic factors with blood glucose being the most important. As mentioned above, increased blood glucose levels stimulate the release of insulin. Insulin secretion is also stimulated by amino acids and is important in using these for protein synthesis. Catecholamines such as  adrenal epinephrine inhibit insulin secretion during stress. this is important so that glucose can be used by tissues that are active during stress response. 


Insulin is also involved in an important feedback loop with glucagon whereby increased glucagon stimulates insulin secretion from the beta cells of the pancreas and insulin then subdues glucagon secretion from the alpha cells. (Hadley and Levine 252-253)


Diabetes Mellitus is a disease characterized by high glucose levels in the blood resulting from a lack or resistance to insulin. It causes symptoms such as frequent urination and increased thirst. Left untreated, increased blood glucose greatly damages blood vessels leading to complications such as heart disease, possible amputations, blindness and death.


  Type 1 diabetes also known as insulin-dependent diabetes mellitus occurs when there is a decrease in the number of insulin containing beta cells within the pancreas. This may occur due to a hereditary predisposition or to the development of islet cell surface antibodies, however the signals responsible for production of these antibodies are unknown. There is evidence to suggest that type 1 juvenile onset diabetes can be caused by a virus or symptoms can manifest as a result of damage sustained by infections such as mumps or rubella. Onset of Type 1 diabetes usually occurs early in life. Juvenile onset diabetes occurs in youth where symptoms develop suddenly.  Type 1 diabetes is typically treated with regulated insulin injections. Insulin can not be taken orally since it is a protein and would be digested.  (Hadley and Levine 255-256).

http://gconnect.in/gc/lifestyle/let-natural-health-deal-with-your-diabetes.html

Type 2 diabetes is also known as non-insulin dependent diabetes mellitus arrises not from a lack of insulin as in type 1, but a reduced sensitivity of target tissues to the action of insulin. This is referred to as insulin resistance. Patients with Type 2 diabetes often have hyperinsulinemia, which is an elevation in blood insulin levels as a result of over secretion from the pancreas due to elevated blood glucose. Since target tissues are less sensitive to insulin, blood glucose levels remain high despite the increases in insulin . Type 2 diabetes was formerly referred to as adult onset diabetes because it was typically found in middle age adults who were obese or overweight. However, due to the increase incidence of obesity in children, there has been an increase in occurrence of type 2 diabetes in younger individuals. Therefore Type 2 diabetes is no longer referred to as an adult onset disease. Type 2 diabetes is responsible for approximately 90% of diabetes cases. It is often the result of poor lifestyle choices including bad diet and lack of exercise. This results in frequent high blood glucose levels and either not enough insulin to make up for it or an increased insensitivity of cells to insulin. Type 2 diabetes can thus be treated by improving one's lifestyle by managing diet and increasing exercise.  (Hadley and Levine 256-257).

http://www.topnews.in/health/early-weight-loss-helps-patients-control-type-2-diabetes-23934

References: 

Hadley, Mac E., and Jon E. Levine. Endocrinology. 6th ed. Upper Saddle River, NJ: Pearson, 2006. 241,243, 252-253, 255-257. Print. 


http://gconnect.in/gc/lifestyle/let-natural-health-deal-with-your-diabetes.html


http://www.topnews.in/health/early-weight-loss-helps-patients-control-type-2-diabetes-23934