7 research outputs found
Effects of subtotal pancreatectomy and longâterm glucose and lipid overload on insulin secretion and glucose homeostasis in minipigs
Abstract Introduction Nowadays, there are no strong diabetic pig models, yet they are required for various types of diabetes research. Using cuttingâedge techniques, we attempted to develop a type 2 diabetic minipig model in this study by combining a partial pancreatectomy (Px) with an energetic overload administered either orally or parenterally. Methods Different groups of minipigs, including Göttingenâlike (GL, nâ=â17) and Ossabaw (O, nâ=â4), were developed. Prior to and following each intervention, metabolic assessments were conducted. First, the metabolic responses of the Göttingenâlike (nâ=â3) and Ossabaw (nâ=â4) strains to a 2âmonth HighâFat, HighâSucrose diet (HFHSD) were compared. Then, other groups of GL minipigs were established: with a single Px (nâ=â10), a Px combined with a 2âmonth HFHSD (nâ=â6), and longâterm intraportal glucose and lipid infusions that were either preceded by a Px (nâ=â4) or not (nâ=â4). Results After the 2âmonth HFHSD, there was no discernible change between the GL and O minipigs. The pancreatectomized group in GL minipigs showed a significantly lower Acute Insulin Response (AIR) (18.3â±â10.0âIU/mL after Px vs. 34.9â±â13.7âIU/mL before, pâ<â.0005). In both longâterm intraportal infusion groups, an increase in the Insulinogenic (IGI) and Hepatic Insulin Resistance Indexes (HIRI) was found with a decrease in the AIR, especially in the pancreatectomized group (IGI: 4.2â±â1.9 after vs. 1.5â±â0.8 before, pâ<â.05; HIRI (Ă10â5): 12.6â±â7.9 after vs. 3.8â±â4.3 before, pâ<â.05; AIR: 24.4â±â13.7â”IU/mL after vs. 43.9â±â14.5â”IU/mL before, pâ<â.005). Regardless of the group, there was no fasting hyperglycemia. Conclusions In this study, we used pancreatectomy followed by longâterm intraportal glucose and lipid infusions to develop an original minipig model with metabolic syndrome and early signs of glucose intolerance. We reaffirm the pig's usefulness as a preclinical model for the metabolic syndrome but without the fasting hyperglycemia that characterizes diabetes mellitus
Innovative transdermal delivery of insulin using gelatin methacrylate-based microneedle patches in mice and mini-pigs
International audiencePainless and controlled on-demand drug delivery is the ultimate goal for the management of various chronic diseases, including diabetes. , Painless and controlled on-demand drug delivery is the ultimate goal for the management of various chronic diseases, including diabetes. To achieve this purpose, microneedle patches are gaining increased attention. While degradable microneedle (MN) arrays are widely employed, the use of non-dissolving MN patches remains a challenge to overcome. In this study, we demonstrate that crosslinking gelatin methacrylate with polyethylene glycol diacrylate (PEGDA) is potent for engineering non-dissolving MN arrays. Incorporation of MoS 2 nanosheets as a photothermal component into MN hydrogels results in MNs featuring on-demand release properties. An optimized MoS 2 -MN array patch formed using a hydrogel solution containing 500 ÎŒg mL â1 of MoS 2 and photochemically crosslinked for 5 min shows required mechanical behavior under a normal compressive load to penetrate the stratum corneum of mice or pig skin and allows the delivery of macromolecular therapeutics such as insulin upon swelling. Using ex vivo and in vivo models, we show that the MoS 2 -MN patches can be used for loading and releasing insulin for therapeutic purposes. Indeed, transdermal administration of insulin loaded into MoS 2 -MN patches reduces blood glucose levels in C57BL/6 mice and mini-pigs comparably to subcutaneously injected insulin. We believe that this on-demand delivery system might alter the current insulin therapies and might be a potential approach for delivery of other proteins
The GLP1R Agonist Liraglutide Reduces Hyperglucagonemia Induced by the SGLT2 Inhibitor Dapagliflozin via Somatostatin Release
A Single Dose of Oral Metformin Reduces the Post-Prandial Glucose Response Through a Transient Modulation of Apical Sodium-Glucose Co-Transporter
Oral metformin transiently lowers post-prandial glucose response by reducing the apical expression of sodium-glucose co-transporter 1 in enterocytes
Summary: Metformin (MET) is the most prescribed antidiabetic drug, but its mechanisms of action remain elusive. Recent data point to the gut as METâs primary target. Here, we explored the effect of MET on the gut glucose transport machinery. Using human enterocytes (Caco-2/TC7 cells) in vitro, we showed that MET transiently reduced the apical density of sodium-glucose transporter 1 (SGLT1) and decreased the absorption of glucose, without changes in the mRNA levels of the transporter. Administered 1 h before a glucose challenge in rats (Wistar, GK), C57BL6 mice and mice pigs, oral MET reduced the post-prandial glucose response (PGR). This effect was abrogated in SGLT1-KO mice. MET also reduced the luminal clearance of 2-(18F)-fluoro-2-deoxy-D-glucose after oral administration in rats. In conclusion, oral metformin transiently lowers post-prandial glucose response by reducing the apical expression of SGLT1 in enterocytes, which may contribute to the clinical effects of the drug