Aims/hypothesis Adult beta cells have a diminished ability to proliferate. Phosphatase and tensin homologue (PTEN) is a lipid phosphatase that antagonises the function of the mitogenic phosphatidylinositol 3-kinase (PI3K) pathway. The objective of this study was to understand the role of PTEN and PI3K signalling in the maintenance of beta cells postnatally. Methods We developed a Ptenlox/lox; Rosa26lacZ; RIP-CreER+ model that permitted us to induce Pten deletion by treatment with tamoxifen in mature animals. We evaluated islet mass and function as well as beta cell proliferation in 3- and 12-month-old mice treated with tamoxifen (Pten deleted) vs mice treated with vehicle (Pten control). Results Deletion of Pten in juvenile (3-month-old) beta cells significantly induced their proliferation and increased islet mass. The expansion of islet mass occurred concomitantly with the enhanced ability of the Pten-deleted mice to maintain euglycaemia in response to streptozotocin treatment. In older mice (>12 months of age), deletion of Pten similarly increased islet mass and beta cell proliferation. This novel finding suggests that PTEN-regulated mechanisms may override the age-onset diminished ability of beta cells to respond to mitogenic stimulation. We also found that proteins regulating G1/S cell-cycle transition, such as cyclin D1, cyclin D2, p27 and p16, were altered when PTEN was lost, suggesting that they may play a role in PTEN/PI3K-regulated beta cell proliferation in adult tissue. Conclusions/interpretation The signals regulated by the PTEN/PI3K pathway are important for postnatal maintenance of beta cells and regulation of their proliferation in adult tissues.

Sharma N, Bhat AD, Kassa AD, Xiao Y, Arias EB, Cartee GD. Improved insulin sensitivity with calorie restriction does not require reduced JNK1/2, p38, or ERK1/2 phosphorylation in skeletal muscle of 9-month-old rats. Am J Physiol Regul Integr Comp Physiol 302: R126 -R136, 2012. First published October 19, 2011 doi:10.1152/ajpregu.00372.2011.-Calorie restriction [CR; ϳ40% below ad libitum (AL) intake] improves the health of many species, including rats, by mechanisms that may be partly related to enhanced insulin sensitivity for glucose disposal by skeletal muscle. Excessive activation of several mitogen-activated protein kinases (MAPKs), including JNK1/2, p38, and ERK1/2 has been linked to insulin resistance. Although insulin can activate ERK1/2, this effect is not required for insulin-mediated glucose uptake. We hypothesized that skeletal muscle from male 9-mo-old Fischer 344/Brown Norway rats CR (35-40% beginning at 3 mo old) versus AL rats would have 1) attenuated activation of JNK1/2, p38, and ERK1/2 under basal conditions; and 2) no difference for insulin-induced ERK1/2 activation. In contrast to our hypothesis, there were significant CR-related increases in the phosphorylation of p38 (epitrochlearis, soleus, and gastrocnemius), JNK1 (epitrochlearis and soleus), and JNK2 (gastrocnemius). Consistent with our hypothesis, CR did not alter insulin-mediated ERK1/2 activation. The greater JNK1/2 and p38 phosphorylation with CR was not attributable to diet effects on muscle oxidative stress (assessed by protein carbonyls and 4-hydroxynonenal protein conjugates). In muscles from the same rats used for the present study, we previously reported a CR-related increase in insulin-mediated glucose uptake by the epitrochlearis and the soleus (Sharma N, Arias EB, Bhat AD, Sequea DA, Ho S, Croff KK, Sajan MP, Farese RV, Cartee GD. Am J Physiol Endocrinol Metab 300: E966 -E978, 2011). The present results indicate that the improved insulin sensitivity with CR is not attributable to attenuated MAPK phosphorylation in skeletal muscle.

ABSTRACT. The distribution of retinal blood vessels in the eye of buffalo was studied macroscopically and microscopically in twenty-two eyes of healthy animals. After macroscopic observation, 12 of 22 eyes were used for histological study. Ten eyes were stained with hematoxylin and eosin and two eyes with PAS stain. The present findings revealed that the eye of the buffalo was characterized by the complex network of retinal blood vessels (holangiotic or euangiotic). The central retinal artery and vein pierced the eye through the optic disc and gave off several branches. There were four pairs of primary vessels that were named dorsal, ventral, nasal and temporal retinal arteries and veins. The veins anastmosed with each other at the optic disc to form a somewhat circle. Three patterns of the distribution of blood vessels were described. The distribution of the arteries and veins was the same. KEY WORDS: buffalo, retinal blood vessel.