We detected the FFAR protein with a molecular mass of

We detected the FFAR2 protein with a molecular mass of about 50 kDa, which is comparable to the main band detected in pigs (Li et al., 2014) but different from the calculated size based on the sequence (Wang et al., 2009). The size difference can be explained, at least in part, by glycosylation sites, which are predicted by the NetNGlyc 1.0 server (http://www.cbs.dtu.dk, 2015/11/17), and the specificity was confirmed by the specific blocking peptide. The abundance of FFAR2 protein increased over time during the peripartal period. However, Friedrichs et al. (2014) did not find any changes in the NVP-CGM097 of FFAR2 mRNA in the liver of dairy cows during the peripartal period. Bovine FFAR2 has a lower affinity for acetate and propionate than human FFAR2 (Hudson et al., 2012). Despite this, the concentration of propionate and butyrate in the portal vein (Lomax and Baird, 1983; Casse et al., 1994; Benson et al., 2002) reaches the half-maximal effective concentration (EC50) to activate the receptor, respectively. The portal vein concentrations indicate that the percentage of activation of this receptor in liver might be higher than its activation in other bovine tissues such as adipose tissue, because of lesser blood concentrations of butyrate and propionate in the periphery because of their percentage of hepatic extraction. However, the physiological significance of this receptor for liver metabolism has not been studied previously. Based on the number of animals in the current study, the correlation analysis may not be meaningful. However, it supports the decision to group by BHB level and reveals possibly contrasting associations of the two receptors with metabolic regulation during the peripartal period.
ACKNOWLEDGMENTS
Introduction Diabetes is a heterogeneous disease with the obvious lowest common denominator of hyperglycemia as its main manifestation. The comprehensive disease phenotypes can be very different, especially when considering the dissimilarities of classical Type 1 and Type 2 diabetes. It is generally acknowledged today that one of the most common chronic diseases of the 21st century type 2 diabetes, is a mixture of pathogenetically diverse structures [1]. However, there is one common feature in all the pathological processes that yield abnormally elevated blood glucose: dysfunction of beta-cells resulting in the decline of insulin production and secretion. Even if most type 2 diabetes phenotypes are related to phenomena such as obesity and insulin resistance, restoration of the full potential of insulin secretion would lead to a remission of diabetes. In turn, as the relatively high rate of diabetes relapse after bariatric surgery [2] suggests, deteriorating beta-cell function would often prevail despite an improved metabolic milieu. Therefore, understanding the decline of beta-cells and finding ways to improve their function are essential in combating the disease. This review will examine examples for the impact of interactions between metabolic and genetic alterations in insulin secretion to envision a more efficient diabetes therapy on our way from conventional to personalized medicine. It will focus on genetic and metabolic interactions on incretin and free fatty acid (FFA) induced insulin secretion.
Regulation of insulin secretion The regulation of insulin secretion in the beta-cell is primarily determined by plasma glucose concentration, which triggers the process generally known as glucose-stimulated insulin secretion (GSIS) [3]. However, other fuels such as FFAs and amino acids are also able to act as potent enhancers of insulin secretion. Beside fuels, specific hormones are capable of modulating insulin secretion in the beta-cell. The most important stimulators are incretins, namely glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide, formerly also known as gastric inhibitory polypeptide (GIP). They are secreted upon food stimuli by L- and K-cells of the gastrointestinal tract, respectively, contribute to as much as 70% of insulin secretion after a meal [4] and are widely used as medical treatment of diabetes.