Resistin is a protein that was first discovered in Pennsylvania at the turn of the 21st Century. It’s a protein rich in cysteine, which is present throughout human bodies as well as other animals such as dogs, primates, and pigs.
It is often referred to as ADSF, which stands for adipose tissue-specific secretory factor. Furthermore, it’s also known as C/EBP, which stands for epsilon-regulated myeloid-specific secreted cysteine-rich protein.
Mechanism & Interactions
Resistin takes part in the inflammatory response. It increases the expression of some proinflammatory cytokines. These can include several interleukins and TNF-alpha. It also regulates components occupied in chemotactic pathways which are involved in the recruitment of leukocytes to the site of infection.
As resistin is known to contribute to insulin resistance, this may suggest that resistin could be a link between inflammation and insulin resistance, which are well known to be associated together.
After consideration of these points, it is expected that, if resistin is indeed a link between obesity and type 2 diabetes, while also contributing to the inflammatory response, we should find increases in chronic inflammation in association with obesity and insulin resistance. This can be backed up by recent data which has shown there have been positive correlations between obesity, insulin resistance, and chronic inflammation. Resistin signalling is believed to direct, in part, chronic inflammation.
As well as having an effect on inflammation, resistin is also known to have direct involvement with type 2 diabetes. Resistin primarily acts with bodily tissues, most notably the ones present in the liver. When resistin is present, human tissues don’t see the full effects of insulin. It causes the tissues to become less sensitive. As a consequence, there is an increase in glycogenolysis and gluconeogenesis. This results in there being an enlarged blood glucose levels, which is a telltale sign of type 2 diabetes.
Furthermore, while resistin is largely secreted from macrophages, it is also known to be secreted from fat cells. There is a lot of scientific evidence to suggest a correlation between raised resistin levels and obesity, along with type 2 diabetes. Humans suffering from obesity will have an increased number of fat cells. This results in more resistin being secreted, which desensitizes the bodily tissue, increasing glucose levels, and causing diabetes.
Resistin is made up of various noncovalent interactions between multiple subunits within the protein. When a closer look is taken at each subunit, it’s found that they contain a ‘head’ and ‘tail’ segment. At the head, it is a carboxy-terminal that’s rich in disulphide. The tail is made up of alpha-helices and is an amino-terminal. The tail segments connect to one another, forming a coil with three strands. Tail to tail hexamers are also formed due to an interchain of disulphide linkages.
There are a total of five disulphide bonds formed in the globular domain from resistin. These are Cys35-Cys88, Cys47-Cys87, Cys56-Cys73, Cys58-Cys75, and finally; Cys62-Cys77). By looking at these bonds, it is suggested that there will be conservation of the disulphide pattern.