The Pathophysiology of Type 2 Diabetes Mellitus

Type 2 DM is characterized by insulin insensitivity as a result of insulin resistance, declining insulin <br />
production, and eventual pancreatic beta-cell failure. This leads to a decrease in glucose transport into <br />
the liver, muscle cells, and fat cells. There is an increase in the breakdown of fat with hyperglycemia. The <br />
involvement of impaired alpha-cell function has recently been recognized in the pathophysiology of type <br />
2 DM. As a result of this dysfunction, glucagon and hepatic glucose levels that rise during fasting are not <br />
suppressed with a meal. Given inadequate levels of insulin and increased insulin resistance, <br />
hyperglycemia results. The incretins are important gut mediators of insulin release, and in the case of <br />
GLP-1, of glucagon suppression. Although GIP activity is impaired in those with type 2 DM, GLP1 <br />
insulinotropic effects are preserved, and thus GLP-1 represents a potentially beneficial therapeutic <br />
option. However, like GIP; GLP-1 is rapidly inactivated by DPP-IV in vivo. Two therapeutic approaches to <br />
this problem have been developed: GLP-1 analogues with increased half-lives, and DPPIV inhibitors, <br />
which prevent the breakdown of endogenous GLP1 as well as GIP. Both classes of agents have shown <br />
promise, with potential not only to normalize fasting and postprandial glucose levels but also to improve <br />
beta-cell functioning and mass. Studies are ongoing on the role of mitochondrial dysfunction in the <br />
development of insulin resistance and etiology of type 2 DM. Also very important is adipose tissue, as <br />
endocrine organ hypothesis (secretion of various adipocytokines, i.e., leptin, TNFalpha, resistin, and <br />
adiponectin implicated in insulin resistance and possibly beta-cell dysfunction). A majority of individuals <br />
suffering from type 2 DM are obese, with central visceral adiposity. Therefore, the adipose tissue plays a <br />
crucial role in the pathogenesis of type 2 DM. Although the predominant theory used to explain this link <br />
is the portal/visceral hypothesis giving a key role in elevated non-esterified fatty acid concentrations, <br />
two new emerging theories are the ectopic fat storage syndrome (deposition of triglycerides in muscle, <br />
liver and pancreatic cells). These two hypotheses constitute the framework for the study of the interplay <br />
between insulin resistance and betacell dysfunction in type 2 DM as well as between our obesogenic <br />
environment and DM risk in the next decade.<br />
1. What is the main topic of this passage?<br />
2. Re-write this passage in your own words<br />
3. Find the passive voice in this passage! (write down the sentence and give a bold on the passivevoice form)​

The Pathophysiology of Type 2 Diabetes Mellitus