Barrels XXXI comes to the inland empire

The 31st annual Barrels meeting was held on the campus of the University of California, Riverside on the first two days of November, 2018. The meeting focuses on the whisker to cortical barrel pathway and the systems it impacts. This year’s meeting focussed on the neural mechanisms of motor control, the functions of higher order thalamic nuclei and adaptable perception and decision-making.     

Ameliorative Effects of Oral Glucosamine on Insulin Resistance and Pancreatic Tissue Damage in Experimental Wistar rats on a High-fat Diet

Hyperlipidemia due to a high-fat diet (HFD) is a risk factor for inducing insulin resistance (IR) and adverse effects on pancreatic β-cells in obesity and type 2 diabetes mellitus. This relationship may be due to activation of the hexosamine-biosynthesis pathway. Administration of exogenous glucosamine (GlcN) can increase the end product of this pathway (uridine-5′-diphosphate-N-acetyl-glucosamine), which can mediate IR and protein glycosylation. The objective of this study was to evaluate the effects of oral GlcN and HFD on IR and pancreatic histologic damage in a 22 wk study of 4 groups of male Wistar rats: control group with normal chow diet, HFD group (24%. g/g lard), GlcN group (500 mg/kg⁻¹ per day of glucosamine hydrochloride in drinking water) and HFD plus oral GlcN. Metabolic variables related to IR that were measured included triglycerides (TG), free fatty acids (FFAs) and malondialdehyde (MDA). Histopathologic evaluation of the pancreas was also performed. The results showed IR in the HFD group, which had increased pancreatic nuclear pyknosis and vacuolization, with fatty infiltration and structural alteration of the islets of Langerhans. TG, FFAs and MDA were higher in serum and pancreatic tissue as compared with the control group. The GlcN group did not develop IR and had only mild nuclear pyknosis with no significant change in the pancreatic content of TG, FFAs and MDA. However, the combined administration of GlcN and HFD attenuated IR and improved TG, FFAs and MDA levels in serum and pancreatic tissue and the pancreatic histopathologic changes, with no significant differences as compared with the control group. These findings suggest that the oral GlcN at a dose of 500 mg/kg⁻¹ is protective against IR and the pancreatic histologic damage caused by HFD.

Obesity, which is an insulin resistance (IR) factor, occurs because of excess caloric intake. Clinically, obesity is associated with high levels of free fatty acids (FFAs) in plasma due to the reduced suppression of lipolysis, is associated with conditions such as diabetes type 2 mellitus, hypertension, atherosclerosis, and metabolic syndrome,² and is an important factor in the pathogenesis of long-term organic damage.³⁶ A previous study⁴⁹ reported that an alteration in the ability of adipocytes to store excess calories as triglycerides (TG) contributes to a greater accumulation of lipids and their metabolites in other tissues. These tissues are not necessarily adapted to their storage, resulting in cellular abnormalities such as apoptosis, oxidative stress, and endoplasmic reticulum stress, which alter cell function. However, both hyperlipidemia and hyperglycemia can have harmful effects on cell function, termed lipotoxicity and glucotoxicity, respectively.^1,36 These effects can lead to desensitization of the target peripheral tissues to the biologic actions of insulin and can also induce an insufficient response of the β cells of the pancreas by glucose stimulation.High-fat diets (HFD) have been associated with hyperlipidemia,³² which in turn leads to IR and pathologic consequences in the pancreas. Hyperlipidemia causes overactivation of the hexosamine biosynthesis pathway (HBP) and overexpression of glutamine:fructose-6-phosphate amidotransferase (GFAT); these give rise to uridine-5′-diphosphate-N-acetyl-glucosamine (UDP-GlcNAc), which causes both IR and alteration of protein glycosylation, leading to selective pancreatic cell destruction.^10,25,44 This pathway can also be activated by administration of exogenous glucosamine (GlcN), suggesting that GlcN in relatively high doses can lead to IR both in vitro and in vivo⁴¹ through an inhibitory effect on early insulin signal transduction,¹⁵ The diabetogenic effect, which is caused in part by interference with glucose utilization in pancreatic cells, reduces insulin release. However, other work²⁰ has argued that exogenous GlcN promotes the development of embryonic pancreatic cells, but did not study pancreatic damage due to subchronic infusion of GlcN in vivo.Although exogenous GlcN is widely used for the treatment of osteoarthritis,^4,40,51 the combination of GlcN with a HFD increases plasma FFAs that can induce IR and affect pancreatic tissue. The objective of the present study was to evaluate the long-term effect of oral GlcN on IR and on pancreatic histopathologic changes produced by a HFD in rats.     

Alterations induced by large doses of furosemide in chronic renal insufficiency.

Eleven patients with different degrees of renal failure with creatinine clearances between 7 and 32 ml/min have been studied. After a standard water overload and control periods of clearances, furosemide 1 g was given/i.v. There followed significant increase of renal plasma flow and glomerular filtration rate. In one case the increase was maintained during a follow up period of 3 hours. A significant increase was evident in phosphate, uric acid, sodium, potassium, and calcium clearances, as well as an increase in the sodium delivery to the distal nephron and a decrease in tubular reabsorption of phosphate. All this may be interpreted as the result of renal vasodilation induced by furosemide and its effect upon the proximal tubule and on Henle's loop.