Type 2 diabetes is, for the vast majority of patients, a condition caused by being significantly overweight. Age does has an influence on the risk of being overweight leading to metabolic syndrome and then type 2 diabetes; it is reasonable to say that type 2 diabetes is an age-related condition. In essence, the younger you are, the more fat tissue it requires to push your metabolism over the red line. A few years back, researchers demonstrated that it is specifically fat in the pancreas that causes type 2 diabetes. Of course the only way to put that fat into the pancreas in the normal course of affairs is to become very overweight, creating fat tissue around all of the organs important to metabolism, and negatively influencing their function.
Now, a few years down the line, and as a result of the rapid growth of interest in senescent cells as a cause of aging and age-related disease, we know that (a) excess visceral fat tissue produces chronic inflammation through, among other mechanisms, a more rapid generation of senescent cells, and (b) much of the detrimental effects of type 2 diabetes appear to be mediated by the presence of senescent cells in the pancreas. Treating animals with senolytic drugs reverses many of the effects of the condition. So this all ties together quite nicely as a view of how and why type 2 diabetes occurs. Given that cellular senescence becomes more prevalent in older individuals, that also fits.
While I'm sure that there will be, soon enough, tremendous interest in senolytic therapies from the sizable overweight and diabetic population of the wealthier portions of the world, it remains the case that the most reliable approach to reversing type 2 diabetes, even at the later stages, is to lose the excess weight. Excess visceral fat tissue is required to maintain that harmful fat in the pancreas, and losing weight removes it. Fasting and very low calorie diets also seem quite effective at removing fat from the pancreas, perhaps more rapidly than would occur just by losing the visceral fat tissue via the usual, slow calorie deficit method, based on human trials of this approach.
Fatty liver has been thoroughly investigated as a known and frequently occurring disease. However, little is known about excess weight-induced fat accumulation in the pancreas and its effects on the onset of type 2 diabetes. Researchers have now found that overweight mice prone to diabetes have a high accumulation of fat cells in the pancreas. Mice resistant to diabetes due to their genetic make-up despite excess weight had hardly any fat in the pancreas, but instead had fat deposits in the liver.
The team of scientists divided the overweight animals, which were prone to diabetes, into two groups: The first group was allowed to eat ad libitum - as much as they wanted whenever they wanted. The second group underwent an intermittent fasting regimen: one day the rodents received unlimited chow and the next day they were not fed at all. After five weeks, the researchers observed differences in the pancreas of the mice: Fat cells accumulated in group one. The animals in group two, on the other hand, had hardly any fat deposits in the pancreas.
In order to find out how fat cells might impair the function of the pancreas, researchers isolated adipocyte precursor cells from the pancreas of mice for the first time and allowed them to differentiate into mature fat cells. If the mature fat cells were subsequently cultivated together with the Langerhans islets of the pancreas, the beta cells of the islets increasingly secreted insulin. "We suspect that the increased secretion of insulin causes the Langerhans islets of diabetes-prone animals to deplete more quickly and, after some time, to cease functioning completely. In this way, fat accumulation in the pancreas could contribute to the development of type 2 diabetes."
Ectopic fat accumulation in the pancreas in response to obesity and its implication on the onset of type 2 diabetes remain poorly understood. Intermittent fasting (IF) is known to improve glucose homeostasis and insulin resistance. However, the effects of IF on fat in the pancreas and β-cell function remain largely unknown. Our aim was to evaluate the impact of IF on pancreatic fat accumulation and its effects on islet function.
New Zealand Obese (NZO) mice were fed a high-fat diet ad libitum (NZO-AL) or fasted every other day (intermittent fasting, NZO-IF) and pancreatic fat accumulation, glucose homoeostasis, insulin sensitivity, and islet function were determined and compared to ad libitum-fed B6.V-Lepob/ob (ob/ob) mice. To investigate the crosstalk of pancreatic adipocytes and islets, co-culture experiments were performed.
NZO-IF mice displayed better glucose homeostasis and lower fat accumulation in both the pancreas (-32%) and the liver (-35%) than NZO-AL mice. Ob/ob animals were insulin-resistant and had low fat in the pancreas but high fat in the liver. NZO-AL mice showed increased fat accumulation in both organs and exhibited an impaired islet function. Co-culture experiments demonstrated that pancreatic adipocytes induced a hypersecretion of insulin and released higher levels of free fatty acids than adipocytes of inguinal white adipose tissue.