Department of Paraclinical Sciences, University of Pretoria
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info@myolab.co.za

Obesity, lifestyle and insulin resistance

Introduction


Humans today are leading a more sedentary lifestyle. Moreover, the typical urbanised diet is rich in refined sugars and processed foods. Our lifestyle choices have led to an obesity epidemic. And to top it all, obesity is now recognised as the primary cause of insulin resistance and type II diabetes.

What is the big deal with blood glucose levels?


In all mammals, glucose is a very important fuel to produce energy. The normal blood glucose range in humans should be between 4.5 and 5.5 mmol/l. A key regulator of blood glucose concentrations is the hormone insulin, secreted by the pancreas. Various organs in the body, such as the brain, rely on a constant supply of glucose, with mechanisms in place to ensure a constant supply. In a fasted state, the liver can make glucose from a process called gluconeogenesis and release it into the blood stream.


Eating carbohydrate (e.g. the sugar in your tea, starchy foods) is another means of replenishing glucose. However, this eating of carbohydrate results in a major spike in blood glucose levels, and it is this high level of glucose that can cause problems. Thus, the pancreas secretes insulin that allows tissues, especially fat and skeletal muscle, to rapidly take up the excess glucose, resulting in blood glucose concentrations returning to normal.


What brings about insulin resistance and type II diabetes?


To effectively lower blood glucose, insulin needs to bind to insulin receptors located on the outside membrane of fat and skeletal muscle cells. Once bound, it signals for these tissues to start taking up the glucose into the cells. The term insulin resistance means that the hormone insulin is not effective enough to lower blood glucose. This is not from low insulin concentrations, but rather that some of the insulin receptors located on the membranes of the cells, does not work anymore. The result is that it takes longer for the blood glucose levels to return to normal, which can have other negative effects on the body.


The primary reason for the insulin receptor destruction is frequently high concentrations of blood glucose. In other words, eating too frequently during the day and too much of certain foods can lead to insulin resistance. There are various degrees of insulin resistance and the good news is that it can be reversed. On the other hand, if there is no intervention, the pancreas cells that produce the insulin, starts to fail, eventually leading to no insulin secretion. This latter is called type II diabetes.


What about animals?


Interestingly, the incidence of overweight and obesity has similarly infiltrated the animal kingdom – from domestic pets to wild animals in zoos, those in sanctuaries or those roaming around freely. A major contributing factor to this rise in overweight animals is that their nutritional needs are poorly understood. This lack in knowledge may therefore lead to the overfeeding of animals in captivity with devastating consequences.


Some animals are very smart in finding palatable foods (e.g. racoons and non-human primates such as baboons and monkeys). Once they find a source of tasty food (e.g. breads, biscuits, sugar, etc.) they often become addicted and sow havoc in urban areas – to no fault of themselves. However, very little is known whether overfeeding may lead to diseases similar to that observed in humans. The MyoLab is currently using innovative techniques to study obesity and insulin resistance in various animals species to help understand how this disease comes about, and how it may be cured.


Current projects


Click on any project to read more about the topic, what we are doing and our findings (if available).


Project
Does muscle physiology play a role in developing insulin resistance in domestic cats and dogs?


In the last decade, diabetes has drastically increased in the human population with obesity and diet being the major risk factors. Similarly, the rate of diabetes has increased in the domestic animal population. Dogs are believed to develop a form of diabetes that is similar to type 1 diabetes. Insulin resistance due to inadequate insulin function has also been observed in dogs. Different breeds show different predispositions to the disease. For example, it seems that Samoyeds, Swedish elkhound, lapphund and poodles are at a higher risk for developing diabetes. Golden retrievers, German shepherds and boxers are at a lower risk for developing the disease. Cats are believed to have a form of diabetes similar to type 2 diabetes in humans with obesity being a major risk factor.


Studying diabetes in cats and dogs is of particular interest to the MyoLab for a number of reasons. Firstly, the mechanisms surrounding this disease and specifically the role of skeletal muscle is poorly understood in domestic animals, especially between different breeds. Secondly, cats and dogs share the same environment as humans and therefore may provide us with insight into the understanding of type 2 diabetes in humans. Lastly, this study fits into the overall aims of the MyoLab, which is to study the structure, metabolism and functionality of the skeletal muscle of various species. This will add to the knowledge gained from our previous and ongoing studies where we look at diabetes in wild felids (such as lions and cheetahs) and primates.


What are we doing?


This study aims to compare the skeletal muscle characterisitcs from clinically diagnosed diabetic cats and dogs of various breeds with healthy cats and dogs. Our sample will include animals from Cape Town, Pretoria and Johannesburg. We aim to investigate the skeletal muscle composition, metabolic profile and glucose disposal capacity in these animals in order to further understand the mechanisms of type 2 diabetes. This may provide veterinarians and animal owners with the necessary knowledge to treat and prevent diabetes in domestic cats and dogs.


Project
Are primates at risk of developing diabetes in the wild?

Primates are intelligent, adaptive and opportunistic that become notoriously well known to local residents and tourists for their skilled and aggressive raiding capabilities in picnic areas, houses and even when breaking-and-entering cars.  In fact, once baboons, confined by loss of natural habitat in an urban environment, have had a taste of the “good life” (the refined carbohydrate-rich Western diet), they become hooked and will do just about anything to satisfy their cravings. 

Havoc sowed in a house in Rooi Els, Western Cape, South Africa.

Most primates are highly intelligent. They learn very quickly and, in some respects, can be extremely sly. To go that far, they may be compared to naughty children, doing anything in their power to obtain the food they so crave. Some researchers have compared this craving to being addicted to drugs! In the Cape Peninsula, baboons primarily raid the suburb’s dust bins, but has also resorted into breaking into people’s homes. From observing their human counterparts, some have even mastered opening car doors and home security gates. Once inside a house, they sow havoc, destroying whatever barrier may prevent them from satisfying their craving. Frequent human-baboon interaction also occurs. 


Many altercations have left humans traumatised, especially as baboons have some of the longest canine teeth for their size (some teeth had a length of 45mm!). Although the males can weigh between 30 and 35 kg, they are physically very strong and does not shy away from attacking humans. Various interventions have been put in place to prevent baboons from getting hold of these food stuffs. But, they learn quickly and methods of keeping the animals at bay is dwindling. Another factor that is exposing these animals to this type of food is human neglect and some deliberately feeding these animals for entertainment purposes.


Are primates at risk of insulin resistance?


Observations of baboons in the Cape Peninsula within the City of Cape Town have hinted that some individuals may in fact be suffering the consequences of poor diet, just as humans are. Baboon monitors (humans that act as baboon police) have even gone as far as to report that some of these regular raiders are becoming overweight and lethargic, and some showing signs of hair- and teeth-loss.


A study conducted in 2012 have also shown that some baboons may have been exposed to viruses that can potentially infect humans (e.g. hepatitis A). Nevertheless, apart from the physical symptoms observed, these baboons that are consuming processed foods high in sugar and fat may also run the risk of developing insulin resistance and type II diabetes.


What are we doing?


This project is investigating whether Cape Towns’ urban baboons are (unknowingly) eating their way towards developing insulin resistance and type II diabetes. We are using various techniques, including blood and skeletal muscle, that can provide semi-quantitive data on the level of insulin resistance. Our aim is to use this data to educate the public on why feeding wild animals have serious consequences. Additionally, we hope that this research would also provide clues to better understand insulin resistance in humans and how to combat this dreadful disease.


Project
Does captivity predispose felids to metabolic syndrome?


The captivity of wild animals is a practice implemented for a number of reasons, but primarily for the protection and conservation of endangered species. Due to limited resources and often a lack of knowledge, these animals are frequently fed the incorrect diets, and secured in enclosures which fail to simulate their natural environments. The dietary needs of felids are not yet well understood and may predispose these animals to metabolic diseases. 


In a group of captive lions in the North West Province in South Africa, body weight was found to be highly skewed as the lions were greatly overweight. Furthermore, as a result of routine feeding, the need for behavioural activities of hunting and chasing prey have been removed, causing these lions to become inactive and rather lethargic.


There are various other felid species, such as caracals, cheetahs, leopards and lynxes, that reside in captivity. Each of these species differ in their biochemical and genetic makeup. They therefore may have different nutritional needs which is essential for their health.


It is well known that physical inactivity and obesity in humans are very clear risk factors for the onset of insulin resistance and type II diabetes, but also other diseases such as cardiovascular disease. These diseases have been observed in various zoo animals that lead a sedentary lifestyle. Considering the overweight lions which are showing signs of reduced physical activity, it is then not surprising that the question “Are these captive felids becoming insulin resistant?” is one of relevance.


What are we doing?


To answer this question, the MyoLab is investigating the muscle metabolism of various obese captive wild animals using mitochondrial respiration, in addition to the activity of several enzymes involved in the various phases of the metabolic pathway. Furthermore, specific proteins involved in insulin signalling pathways, are quantitatively determined. It is of great interest whether this change in lifestyle (i.e. captivity) has had an effect on both the structural composition of muscle and mitochondrial efficiency. Finally, the further understanding gathered on the mechanisms of insulin resistance and the progression to diabetes in the wild animal model may offer a window into the pathophysiology of this disease in the human.