Inflammation, decreased levels of circulating endothelial
nitric oxide (eNO) and
brain-derived neurotrophic factor (
BDNF), altered activity of hypothalamic
neurotransmitters (including
serotonin and vagal tone) and gut
hormones, increased concentrations of
free radicals, and imbalance in the levels of bioactive
lipids and their pro- and anti-inflammatory metabolites have been suggested to play a role in
diabetes mellitus (DM).
Type 1 diabetes mellitus (type 1 DM) is due to autoimmune destruction of pancreatic β cells because of enhanced production of
IL-6 and
tumor necrosis factor-α (TNF-α) and other pro-inflammatory
cytokines released by immunocytes infiltrating the pancreas in response to unknown exogenous and endogenous toxin(s). On the other hand, type 2 DM is due to increased peripheral
insulin resistance secondary to enhanced production of
IL-6 and TNF-α in response to high-fat and/or calorie-rich diet (rich in saturated and trans
fats). Type 2 DM is also associated with significant alterations in the production and action of hypothalamic
neurotransmitters, eNO,
BDNF,
free radicals, gut
hormones, and vagus nerve activity. Thus, type 1 DM is because of excess production of pro-inflammatory
cytokines close to β cells, whereas type 2 DM is due to excess of pro-inflammatory
cytokines in the systemic circulation. Hence, methods designed to suppress excess production of pro-inflammatory
cytokines may form a new approach to prevent both type 1 and type 2 DM.
Roux-en-Y gastric bypass and similar surgeries ameliorate type 2 DM, partly by restoring to normal: gut
hormones, hypothalamic neurotransmitters, eNO, vagal activity, gut microbiota, bioactive
lipids,
BDNF production in the gut and hypothalamus, concentrations of
cytokines and
free radicals that results in resetting
glucose-stimulated
insulin production by pancreatic β cells. Our recent studies suggested that bioactive
lipids, such as
arachidonic acid, eicosapentaneoic
acid, and
docosahexaenoic acid (which are
unsaturated fatty acids) and their anti-inflammatory metabolites:
lipoxin A4, resolvins, protectins, and maresins, may have
antidiabetic actions. These bioactive
lipids have anti-inflammatory actions, enhance eNO,
BDNF production, restore hypothalamic dysfunction, enhance vagal tone, modulate production and action of
ghrelin,
leptin and
adiponectin, and influence gut microbiota that may explain their
antidiabetic action. These pieces of evidence suggest that methods designed to selectively deliver bioactive
lipids to pancreatic β cells, gut, liver, and muscle may prevent type 1 and type 2 DM.