Diabetes In Pigs Research Articles

Camel milk ameliorates diabetes in pigs by preventing oxidative stress, inflammation and enhancing beta cell function.

The purpose of the study was to determine how camel milk affects hyperglycemia, beta-cell function, oxidative stress, and inflammatory markers in type 2 diabetic pigs. Twenty-five (25) pigs were separated into five (5) groups of five pigs each, with five (5) non-diabetic and twenty (20) diabetic pigs in each group. Groups 1 and 2 received distilled water as the standard control and diabetic control groups, respectively, while Groups 3 and 4 received camel milk at 250 mL/day and 500 mL/day, respectively, and Group 5 received metformin at 500mg/day. The experiment lasted ten weeks. At the end of the ten weeks, all the pigs were euthanized. Treatments with camel milk substantially enhance glucose fasting levels by reducing hyperglycemia in diabetic pigs, significant level at (p < 0.05). When pigs given camel milk were compared with untreated diabetic pigs, there was a substantial rise (p < 0.05) in superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH) levels. Also, camel milk substantially lowered the levels of interleukin (IL-1β) and tumour necrosis factor-alpha (TNF-α) in diabetic pig serum. Similarly, immunohistochemical analysis of islet cells revealed an increase in insulin production, implying improved glycemic control and the eventual commitment of glucose to glycolysis. The bioactive-mediated anti-hyperglycemic and insulin release potential of camel milk treatments contributed to improving type 2 diabetes mellitus. Camel milk improved beta-cell function while reducing oxidative stress and inflammation in type 2 diabetic pigs.

Diffuse Glomerular Nodular Lesions in Diabetic Pigs Carrying a Dominant-Negative Mutant Hepatocyte Nuclear Factor 1-Alpha, an Inheritant Diabetic Gene in Humans

Glomerular nodular lesions, known as Kimmelstiel-Wilson nodules, are a pathological hallmark of progressive human diabetic nephropathy. We have induced severe diabetes in pigs carrying a dominant-negative mutant hepatocyte nuclear factor 1-alpha (HNF1α) P291fsinsC, a maturity-onset diabetes of the young type-3 (MODY3) gene in humans. In this model, glomerular pathology revealed that formation of diffuse glomerular nodules commenced as young as 1 month of age and increased in size and incidence until the age of 10 months, the end of the study period. Immunohistochemistry showed that the nodules consisted of various collagen types (I, III, IV, V and VI) with advanced glycation end-product (AGE) and N ε-carboxymethyl-lysine (CML) deposition, similar to those in human diabetic nodules, except for collagen type I. Transforming growth factor-beta (TGF-β) was also expressed exclusively in the nodules. The ultrastructure of the nodules comprised predominant interstitial-type collagen deposition arising from the mesangial matrices. Curiously, these nodules were found predominantly in the deep cortex. However, diabetic pigs failed to show any of the features characteristic of human diabetic nephropathy; e.g., proteinuria, glomerular basement membrane thickening, exudative lesions, mesangiolysis, tubular atrophy, interstitial fibrosis, and vascular hyalinosis. The pigs showed only Armanni-Ebstein lesions, a characteristic tubular manifestation in human diabetes. RT-PCR analysis showed that glomeruli in wild-type pigs did not express endogenous HNF1α and HNF1β, indicating that mutant HNF1α did not directly contribute to glomerular nodular formation in diabetic pigs. In conclusion, pigs harboring the dominant-negative mutant human MODY3 gene showed reproducible and distinct glomerular nodules, possibly due to AGE- and CML-based collagen accumulation. Although the pathology differed in several respects from that of human glomerular nodular lesions, the somewhat acute and constitutive formation of nodules in this mammalian model might provide information facilitating identification of the principal mechanism underlying diabetic nodular sclerosis.

Effects of streptozotocin-induced diabetes in domestic pigs with focus on the amino acid metabolism

Streptozotocin (STZ) given intravenously destroys pancreatic beta cells and is widely used in animal models to mimic type 1 diabetes. The effects of STZ on the clinical state of health and metabolism were studied in six high health certified domestic pigs weighing 19+/-1.3 kg at the start of the experiment. A single STZ dose of 150 mg/kg of body weight successfully induced hyperglycaemia and alterations in amino acid metabolism. Within 9 h after STZ administration, the blood glucose values fell from 5.4-7.5 mmol/L to 0.8-2.2 mmol/L. Hypoglycaemia was treated with 0.5 g glucose/kg body weight. In all pigs, hyperglycaemia was produced 24 h after STZ treatment, and 3 days after STZ injection, the glucose concentration was >25 mmol/L. Mean C-peptide concentration was 0.25+/-0.16 microg/L since 2 days after STZ injection until the end of the study. The serum concentration of the branched-chain amino acids (BCAA) increased four-fold, and alanine and taurine decreased by approximately 70% and 50%, respectively, after STZ treatment. All but one pig remained brisk and the physical examination was normal except for a retarded growth rate and a reduction of the skeletal muscle. At the end of the study, the pigs were moderately emaciated. Postmortem examination confirmed muscle wasting and a reduction of abdominal and subcutaneous fat. In conclusion, STZ-induced diabetes in pigs fulfils the requirements for a good animal model for type 1 diabetes with respect to clinical signs of the disease and alterations in the carbohydrate and amino acid metabolism.

Whole pancreatoduodenal allotransplantation model with jejunum drainage and portal vein drainage for treatment of type I diabetes in pigs

Objective To establish the model of pancreatoduodenal transplantation in pigs with enteric drainage （ED） and portal venous drainage （PVD）. Methods Forty hybrid landraces were randomized into the donor group and recipient group. Pancreatoduodenal allotransplantation was then performed. The donor pigs were perfused via abdominal aorta without clamping the portal venous outflow with UW solution at 80- 100 crnH20 after heparinization. Whole pancreatoduodenal graft was harvested with segments of abdominal aorta and portal vein and shaped under cold UW solution. Then the end-to-end anastomosis was performed with the donor iliac artery bifurcation Y graft to the recipient superior mesenteric arteries and celiac artery. Furthermore, type Ⅰ diabetes model was established by removal of the recipient pancreas. The venous anastomosis was reconstructed between the donor portal vein and the recipient superior mesenteric vein. Meanwhile, the end-to-side anastomosis was performed with the donor common iliac artery bifurcation Y graft to the recipient abdominal aorta and the side-to-side intestinal anastomosis was done between the donor duodenum and the recipient jejunum. External jugular vein was intubated for transfusion. The levels of sugar, insulin and glucagons in blood were determined during the operation and 1, 3, 5 and 7 d after the operation. Results Twenty pigs in the recipient group received pancreatoduodenal allotransplantation. One died from complication of anesthesia. The successful rate was 95.6%. Operative complications occurred in 3 pigs, in which phlebothrombosis accounted for 4. 6%, duodenojejunal anastomotic leakage for 4. 6%. The blood level of sugar decreased and those of insulin and glucagons increased within 30 min and recovered on the 2nd d after removal of the pancreas. Rejection occurred on the 1st d and reached the worst level on the 7th d after transplantation without the changes in blood levels of insulin and glucagons and symptoms of rejection. Conclusions Pancreatoduodenal transplantation in pigs can be used to treat type Ⅰ diabetes. ED and PVD can keep the endocrine function. The technique of duodenal transplantation with ED and PVD may pave the way for further development of pancreatic transplantation in clinical practice. Key words: Transplantation homologous; Pancreas; Operation; Animal model

The effects of birth weight and postnatal growth rate on the development of type 2 diabetes in pigs

Epidemiological studies have linked small birth weight and rapid compensatory growth to a number of chronic diseases, such as type 2 diabetes, hypertension and cardiovascular disease. We used Yucat...

Swine Models of Type 2 Diabetes Mellitus: Insulin Resistance, Glucose Tolerance, and Cardiovascular Complications

In humans, diabetes mellitus (DM) is considered a heterogeneous metabolic disorder. Swine have been used as a model for many human conditions including type 1 (insulin-deficient) and type 2 (insulin-resistant) DM research because of their phenotypic similarities to humans including: cardiovascular anatomy and function, metabolism, lipoprotein profile, size, tendency to obesity, and omnivorous habits. There is phenotypic overlap between the two types of DM and pig models show characteristics and complications of both. Streptozotocin and alloxan have been used to create insulin deficient diabetes in pigs. One of the most unique and useful phenotypes is that these insulin-deficient pigs develop more severe coronary atherosclerosis than nondiabetic controls. It is not fully understood why patients with either type 1 or type 2 DM have increased severity and diffuseness of atherosclerosis compared with nondiabetic patients. The current human epidemic of type 2 DM and its attendant cardiovascular complications underscore the unmet need for creating a useful, readily available animal model of type 2 insulin resistant DM that also develops coronary artery atherosclerosis. The phenotypic susceptibility to coronary atherosclerosis makes pigs an attractive species to identify causative mechanisms. Suggested criteria for validation of an animal model of humanoid type 2 DM are described. The goal would be to develop a useful animal model for mechanistic studies as well as to develop and test novel therapeutics both for type 2 DM as well as its cardiovascular complications.

Insulin-like growth-factor binding protein (IGFBP) serum levels and hepatic IGFBP-2 and -3 mRNA expression in diabetic and insulin-treated swine ( Sus scrofa)

1. 1. Diabetes had no significant effect on IGFBP-3 message and serum levels however, subsequent insulin treatment caused more than a two-fold increase in both hepatic IGFBP-3 mRNA and serum levels above controls ( P < 0.05). 2. 2. The induction of diabetes in pigs significantly increased the steady state levels of IGFBP-2 mRNA in the liver of young swine ( P < 0.05). 3. 3. Both liver message and serum IGFBP-2 were reduced to control levels with insulin therapy. 4. 4. We report here that in addition to its affects on IGFBP-2, insulin is involved in the regulation of IGFBP-3 expression.