Inhibition Of Pancreatic Enzymes Research Articles

Synthesis and Characterization of Alpinia calcarata Loaded Nanoparticles to Control Hyperglycemia

Bovine Serum Albumin (BSA) nanoparticles loaded with the bioactive compounds of A. calcarata, which is known to exert its antidiabetic activity through the inhibition of pancreatic enzymes, are a good form of an antidiabetic nutraceutical as they have reduced side effects, protection of active compounds from environmental agents, specific delivery to target sites and prolonged shelf-life. The objective of the present study was to synthesize and characterize A. calcarata loaded nanoparticles (ALNP) to be used as a powder form nutraceutical with higher antidiabetic activity. In this study an aqueous A. calcarata extract (4.00 mL) was added to BSA (20 mg/mL, 4.00 mL, pH 9) in the presence of citric acid as the cross-linking agent. The ALNP gave an IC50 value of 147 µg/mL, a glucose (5 mM) uptake percentage of 73.09% at a 0.5 mg/mL concentration, a solubility value of 64%, A. calcarata loading percentage of 6.66% and A. calcarata entrapment efficiency of 87.71%. They had a spherical morphology and uniform size with a particle size of 1030.70 nm, PDI of 0.199 and a zeta potential of 2.57 mV. The UV-Visible absorbance spectra and FT-IR spectra showed that citric acid had caused conformational changes in the protein structure of BSA and that the active compounds were successfully loaded into the synthesized nanoparticles which interacted with the protein matrix via covalent bonds. Therefore, it can be concluded that the synthesized nanoparticles have an antidiabetic effect and the antidiabetic activity of bioactive compounds of the aqueous A. calcarata extract become enhanced when loaded onto the nanocarriers.

Impaired Small-Bowel Barrier Integrity in the Presence of Lumenal Pancreatic Digestive Enzymes Leads to Circulatory Shock

In bowel ischemia, impaired mucosal integrity may allow intestinal pancreatic enzyme products to become systemic and precipitate irreversible shock and death. This can be attenuated by pancreatic enzyme inhibition in the small-bowel lumen. It is unresolved, however, whether ischemically mediated mucosal disruption is the key event allowing pancreatic enzyme products systemic access and whether intestinal digestive enzyme activity in concert with increased mucosal permeability leads to shock in the absence of ischemia. To test this possibility, the small intestinal lumen of nonischemic rats was perfused for 2 h with either digestive enzymes, a mucin disruption strategy (i.e., mucolytics) designed to increase mucosal permeability, or both, and animals were observed for shock. Digestive enzymes perfused included trypsin, chymotrypsin, elastase, amylase, and lipase. Control (n = 6) and experimental animals perfused with pancreatic enzymes only (n = 6) or single enzymes (n = 3 for each of the five enzyme groups) maintained stable hemodynamics. After mucin disruption using a combination of enteral N-acetylcysteine, atropine, and increased flow rates, rats (n = 6) developed mild hypotension (P < 0.001 compared with groups perfused with pancreatic enzymes only after 90 min) and increased intestinal permeability to intralumenally perfused fluorescein isothiocyanate-dextran 20 kd (P < 0.05) compared with control and enzyme-only groups, but there were no deaths. All animals perfused with both digestive enzymes and subjected to mucin disruption (n = 6) developed hypotension and increased intestinal permeability (P < 0.001 after 90 min). Pancreatic enzymes were measured in the intestinal wall of both groups subjected to mucin disruption, but not in the enzyme-only or control groups. Depletion of plasma protease inhibitors was found only in animals perfused with pancreatic enzymes plus mucin disruption, implicating increased permeability and intralumenal pancreatic enzyme egress in this group. These experiments demonstrate that increased bowel permeability via mucin disruption in the presence of pancreatic enzymes can induce shock and increase systemic protease activation in the absence of ischemia, implicating bowel mucin disruption as a key event in early ischemia. Digestive enzymes and their products, if allowed to penetrate the gut wall, may trigger multiorgan failure and death.

A New Hypothesis for Microvascular Inflammation in Shock and Multiorgan Failure: Self‐Digestion by Pancreatic Enzymes

Shock is accompanied by a severe inflammatory cascade in the microcirculation, the origin of which has been hypothesized in the past to be associated with specific mediators such as endotoxin, oxygen free radicals, nitric oxide, cytokines, and lipid products. But no intervention with clinical effectiveness has been derived from these ideas to date. The authors propose here a new hypothesis suggesting that degradative enzymes, synthesized in the pancreas as part of normal digestion, may play a central role in shock and multiorgan failure. These powerful enzymes have the ability to digest almost every biological material. Self-digestion (i.e. autodegradation) is prevented by compartmentalizing the fully activated degradative enzymes in the intestinal lumen by the mucosal barrier. In shock, maintenance of the mucosal barrier is impaired and it becomes permeable to pancreatic enzymes. Digestive enzymes thereby gain access to the wall of the intestine and initiate self-digestion of submucosal extracellular matrix proteins and interstitial cells. The process leads to generation and release of a host of strong inflammatory mediators. The authors hypothesize that inhibition of pancreatic enzymes in the lumen of tile intestine can serve to attenuate formation of these inflammatory mediators in ischemic tissues following hemorrhagic shock, and consequently prevent cell and tissue injury as well as multiorgan failure.

Changes in somatostatin receptor expression of the pancreas and effectiveness of octreotide in rats with acute necrotizng pancreatitis

To investigate changes in the expression of the somatostatin receptor (SSTR) of the pancreas and of pancreatic blood flow, and its relationship to the metabolism of eicosanoids in order to elucidate the effectiveness of octreotide, an analog of somatostatin, in acute necrotizing pancreatitis (ANP). A model of ANP was induced in rats with injection of sodium taurocholate via the pancreaticobiliary duct. The SSTR was detected using a radioligand binding assay (RBA) with 125I-somatostatin-14, and the SSTR2 mRNA of the pancreas was analyzed using in situ hybridization. Pancreatic blood flow and the metabolites of eicosanoids were also determined. The SSTR of the pancreas was 109.70 +/- 58.32 fmol/mg protein in normal rats. A significant decrease in the SSTR, together with the signals of SSTR2 mRNA, was shown at 3, 6 and 12 h after onset of ANP. Pancreatic blood flow was reduced and thromboxin-2 was increased significantly in the course of ANP. In the ANP group treated with octreotide, both the decrease in pancreatic blood flow and the abnormal metabolism of eicosanoids were corrected, and the pathological damage was relieved. SSTR expression of the pancreas is significantly reduced in ANP. Correction of the abnormal metabolism of eicosanoids and improvement in pancreatic microcirculation may be the major mechanism of somatostatin analogs in the treatment of ANP and inhibition of pancreatic enzymes via their receptors plays a minor role.