Diabetes mellitus is a common endocrinopathy in cats that is associated with pancreatic islets lesions. Research on isolated islets contributed to the understanding of the pathophysiology of human diabetes. Therefore, by improving the existing methods of isolation in cats, we aimed at increasing islet yield, purity and viability of feline isolated islets. Islet isolation was accomplished by pancreas perfusion with 80ml of Collagenase type IV through the pancreatic duct at the site of the major papilla. The enzymatic digestion was combined with mechanical disruption and controlled by dithizone staining. Purification was performed by filtration and handpicking. Purified islets were plated on extracellular matrix pre-coated plates and cultured for 48h. Feline islets with a high degree of viability and purity were isolated and cultured for the first time. Although the percentage of islet free from the acinar tissue relative to the total number of isolated islets was low compared to other species, the suggested protocol represents a promising progress in the procedure of islet isolation in cats.

Pancreatic amyloidosis and loss of α and β cells have been shown to occur in cats with diabetes mellitus, although the number of studies currently available is very limited. Furthermore, it is not known whether pancreatic islet inflammation is a common feature. The aims of the present study were to characterize islet lesions and to investigate whether diabetic cats have inflammation of the pancreatic islets. Samples of pancreas were collected postmortem from 37 diabetic and 20 control cats matched for age, sex, breed, and body weight. Histologic sections were stained with hematoxylin and eosin and Congo red; double labeled for insulin/CD3, insulin/CD20, insulin/myeloperoxidase, insulin/proliferating cell nuclear antigen, and glucagon/Ki67; and single labeled for amylin and Iba1. Mean insulin-positive cross-sectional area was approximately 65% lower in diabetic than control cats ( P = .009), while that of amylin and glucagon was similar. Surprisingly, amyloid deposition was similar between groups ( P = .408). Proliferation of insulin- and glucagon-positive cells and the number of neutrophils, macrophages, and T (CD3) and B (CD20) lymphocytes in the islets did not differ. The presence of T and B lymphocytes combined tended to be more frequent in diabetic cats ( n = 8 of 37; 21.6%) than control cats ( n = 1 of 20; 5.0%). The results confirm previous observations that loss of β cells but not α cells occurs in diabetic cats. Islet amyloidosis was present in diabetic cats but was not greater than in controls. A subset of diabetic cats had lymphocytic infiltration of the islets, which might be associated with β-cell loss.

Diabetes mellitus is a common endocrinopathy in humans and in cats. The general prevalence of diabetes mellitus, and in particular of type 2 diabetes, has risen dramatically in recent years. This increase has often been linked to the rise in the obesity pandemic because obesity and the ensuing metabolic consequences constitute major risk factors for human type 2 and for feline diabetes. Feline diabetes shares many features of human type 2 diabetes in respect to its pathophysiology, underlying risk factors and treatment strategies. This review will briefly summarize major characteristics in the human and the feline disease and where available, point out the current knowledge on similarities and differences.

Background: The continuous glucose monitoring system (CGMS) Guardian REAL-Time (R) allows the generation of very detailed glucose profiles in cats. The performance of CGMS to generate short-term glucose profiles to evaluate treatment response has not been yet evaluated in diabetic cats. Hypothesis: Analysis of glucose profiles generated using the CGMS produces insulin dose recommendations that differ from those of profiles generated using the portable blood glucose meter (PBGM) in diabetic cats. Animals: Thirteen client-owned diabetic cats. Methods: Prospective, observational study. Simultaneous glucose profiles were generated over an 8-10 hour period using the CGMS, blood glucose concentration was measured every 2 hours with the PBGM. Profiles were submitted to three internal medicine specialists who used them to determine the insulin dose. Differences between insulin doses deduced from paired profiles were compared. Percentages of nadirs recorded with the CGMS that were lower, higher, or equal to those derived with the PBGM were calculated. Results: Twenty-one paired glucose profiles were obtained. There was no difference of insulin doses based on CGMS and PBGM profiles (median 0 U; range: -1 to +0.5). Treatment decisions did not differ among investigators. Compared with the observed PBGM nadir, the CGMS nadir was lower, higher, or equal in 17, 2, and 2 of 21 cases, respectively. Conclusions and Clinical Importance: Adjustments in insulin dose based on glucose profiles generated with the CGMS are similar to those based on the PBGM. The common occurrence of lower nadirs recorded with the CGMS suggests that this device detects hypoglycemic periods that are not identified with the PBGM.

Acute inflammation in humans is associated with transient insulin resistance (IR) and dyslipidemia. Chronic low-grade inflammation is a pathogenic component of IR and adipose tissue dysfunction in obesity-induced type 2 diabetes. Because feline diabetes closely resembles human type 2 diabetes, we studied whether lipopolysaccharide (LPS)-induced subacute inflammation, in the absence of obesity, is the potential primary cause of IR and metabolic disorders. Cats received increasing iv doses (10-1000 ng/kg(-1) · h(-1)) of LPS (n = 5) or saline (n = 5) for 10 d. Body temperature, proinflammatory and metabolic markers, and insulin sensitivity were measured daily. Tissue mRNA and protein expression were quantified on d 10. LPS infusion increased circulating and tissue markers of inflammation. Based on the homeostasis model assessment, endotoxemia induced transient IR and β-cell dysfunction. At the whole-body level, IR reverted after the 10-d treatment; however, tissue-specific indications of IR were observed, such as down-regulation of adipose glucose transporter 4, hepatic peroxisome proliferative activated receptor-γ1 and -2, and muscle insulin receptor substrate-1. In adipose tissue, increased hormone-sensitive lipase activity led to reduced adipocyte size, concomitant with increased plasma and hepatic triglyceride content and decreased total and high-density lipoprotein cholesterol levels. Prolonged LPS-induced inflammation caused acute IR, followed by long-lasting tissue-specific dysfunctions of lipid-, glucose-, and insulin metabolism-related targets; this ultimately resulted in dyslipidemia but not whole-body IR. Endotoxemia in cats may provide a promising model to study the cross talk between metabolic and inflammatory responses in the development of adipose tissue dysfunction and IR.

BACKGROUND Clinical remission is frequent in cats with well-controlled diabetes mellitus, but few studies explored predictors of this phenomenon. HYPOTHESIS Data retrieved from medical records at admission might be valuable to identify likelihood of remission and its duration in diabetic cats. ANIMALS Ninety cats with newly diagnosed diabetes, followed-up until death or remission. METHODS Retrospective cohort study. Data were collected from records at admission, including history, signalment, physical examination, haematology, and biochemical profile, and the occurrence and duration of remission, defined as normoglycemia without insulin for ≥4 weeks. Predictors of remission were studied with univariate and multivariate logistic regression. Factors associated with remission duration were analyzed with Kaplan-Meier and Cox proportional hazard models. RESULTS Forty-five (50%) cats achieved remission, after a median time of 48 days (range: 8-216). By study end, median remission duration was 114 days (range: 30-3,370) in cats that died and 151 days (range: 28-1,180) in alive cats. Remission was more likely with higher age (OR: 1.23, 95% CI: 1.04-1.46; P=.01) and less likely with increased serum cholesterol (OR: 0.36, 95% CI: 0.11-0.87; P=.04). Remission was longer with higher body weight (HR: 0.65, 95% CI: 0.42-0.99; P=.04) and shorter with higher blood glucose (HR: 1.01, 95% CI: 1.00-1.02; P=.02). CONCLUSIONS AND CLINICAL IMPORTANCE Age, body weight, cholesterol, and glucose levels are suggested for prediction of remission or its duration in diabetic cats. Older cats developing diabetes may have a better outcome, possibly suggesting a slower disease progression.

BACKGROUND:The Guardian REAL-Time is a continuous glucose-monitoring system (CGMS) recently developed to provide instantaneous interstitial glucose concentrations; the system does not require a monitor being fixed to the animal.HYPOTHESIS:The CGMS provides accurate and reproducible real-time readings of glucose concentration in cats.ANIMALS:Thirty-two diabetic cats, 2 cats with suspected insulinoma, and 5 healthy cats.METHODS:Prospective, observational study. CGMS accuracy was compared with a reference glucose meter at normal, high, and low blood glucose concentrations using error grid analysis. Reading variability of 2 simultaneously used CGMS was determined in diabetic cats by calculating correlation and percentage of concordance of paired data at different glycemic ranges. The time interval between increasing glycemia and a rise in interstitial fluid glucose measured by the CGMS was assessed in healthy cats receiving glucose IV; the time point of maximal increase in interstitial glucose concentrations was calculated.RESULTS:The CGMS was 100, 96.1, and 91.0% accurate at normal, high, and low blood glucose concentrations. Measurements deviated from reference by -12.7 +/- 70.5 mg/dL at normal, -12.1 +/- 141.5 mg/dL at high, and -1.9 +/- 40.9 mg/dL at low glucose concentrations. Overall, paired CGMS readings correlated significantly (r = 0.95, P < .0001) and concordance was 95.7%. The median delay after IV administration of glucose to an increase in interstitial glucose was 11.4 minutes (range: 8.8-19.7 minutes).CONCLUSIONS AND CLINICAL IMPORTANCE:Although some readings substantially deviated from reference values, the CGMS yields reproducible results, is clinically accurate in cats with hyperglycemia and euglycemia, and is slightly less accurate if blood glucose concentrations are low. Rapidly increasing interstitial glucose after a glycemic rise suggests that the CGMS is suitable for real-time measurement under clinical conditions.

Obesity and hyperlipidemia are associated with impaired insulin sensitivity in human type 2 diabetes mellitus, possibly due to activation of a mild inflammatory response. Because obesity-induced insulin resistance predisposes cats to diabetes and because hyperlipidemia is a frequent concurrent finding, excess lipids may also impair insulin sensitivity in cats. Healthy cats (n=6) were infused with lipids (Lipovenoes 10%) for 10 days to clamp blood triglycerides at the approximate concentration of untreated feline diabetes (3-7 mmol/l). Controls received saline (n=5). On day 10, plasma adiponectin and proinflammatory markers were measured. Whole-body insulin sensitivity was calculated following an intravenous glucose tolerance test. Tissue mRNAs of glucose metabolism-related genes were quantified in subcutaneous and visceral fat, liver, and skeletal muscles. Accumulation of lipids was assessed in liver. At the termination of infusion, whole-body insulin sensitivity did not differ between groups. Compared to saline, cats infused with lipids had 50% higher plasma adiponectin and 2-3 times higher alpha(1)-acid glycoprotein and monocyte chemoattractant protein-1. Unexpectedly, lipid-infused cats had increased glucose transporter-4 (GLUT4) mRNA in the visceral fat, and increased peroxisome proliferative activated receptor-gamma2 (PPARgamma2) in subcutaneous fat; adiponectin expression was not affected in any tissue. Lipid-infused cats developed hepatic steatosis. Although hyperlipidemia induced systemic inflammation, whole-body insulin sensitivity was not impaired after 10 day infusion. Increased circulating adiponectin may have contributed to prevent insulin resistance, possibly by increasing GLUT4 and PPARgamma2 transcripts in fat depots.

In vitro studies point to a toxic effect of high glucose and non-esterified fatty acids on beta cells. Whether elevated levels of glucose and lipids induce beta cell loss in vivo is less clear. The domestic cat has recently been proposed as a valuable animal model for human type 2 diabetes because feline diabetes shows several similarities with diabetes in humans, including obesity-induced insulin resistance, impaired beta cell function, decreased number of beta cells and pancreatic amyloid deposition.

Amylin is a pancreatic hormone that is considered to be a satiating signal acting on neurons of the area postrema (AP) in the hindbrain. The adiposity signals leptin and insulin act in the hypothalamus to influence feeding. They also enhance the hindbrain's responsivity to satiating signals, e.g. cholecystokinin (CCK). The orexigenic hormone ghrelin is thought to use the same hypothalamic pathways as leptin and insulin, with opposite actions on feeding behaviour. In fact, CCK and ghrelin also seem to interact in the control of feeding. Because CCK's anorectic effect depends on endogenous amylin, the aim of this study was therefore to evaluate a possible functional interaction between amylin and these hormones on short-term food intake in rats. The experiments were performed with male Wistar rats. Intracerebroventricular injection (i3vt) of an orexigenic dose of ghrelin (5 ng/5 mu l) reduced but did not completely reverse the intraperitoneal amylin (5 mu g/kg)-induced inhibition of food intake. In comparison, administration of a sub-threshold dose of ghrelin (3 ng/5 mu l) did not affect the anorexigenic action of peripheral amylin. Leptin administered into the third ventricle (i3vt; 3.5 mu g/5 mu l) and intraperitoneal amylin (5 mu g/kg) synergistically reduced food intake in chow-fed rats. I3vt insulin, administered at a sub-threshold dose (0.5 mU/5 mu l), significantly enhanced the response to peripheral amylin. These results indicate that the lipostatic signals leptin and insulin may synergize with amylin to reduce food intake. In contrast, under the conditions tested, the orexigenic hormone ghrelin does not seem to influence the feeding response to peripheral amylin. (C) 2007 Elsevier Inc. All rights reserved.

Amylin is a pancreatic hormone, which is considered a satiating signal acting on neurons of the area postrema (AP). The orexigenic hormone ghrelin and the anorectic hormones leptin and insulin act on specific receptors on neurons in the arcuate nucleus (ARC) of the hypothalamus. These hypothalamic signals have been shown to modulate the effect of peripheral satiating hormones, like cholecystokinin (CCK). Because CCK's anorectic effect depends on endogenous amylin, the aim of this study was therefore to evaluate a possible functional interaction between amylin and these hormones on short-term food intake in rats. The experiments were performed with male Wistar rats using a crossover design. Intracerebroventricular leptin (3.5 μg/5 μl) and intraperitoneal amylin (5 μg/kg) synergistically reduced 1h-food intake by 61% in chow-fed rats (amylin alone: 29%). Insulin administered into the third ventricle (i3vt) at a sub-threshold dose (0.5mU/5 μl) significantly enhanced the response to peripheral amylin, reducing food intake by 69% versus 45% by amylin alone. In contrast, an i3vt injection of an orexigenic dose of ghrelin (5ng/5 μl) did not reverse the intraperitoneal amylin (5 μg/kg)-induced inhibition of food intake, i.e. the difference in food intake between saline and amylin-injected animals was similar after ghrelin administration. The administration of a sub-threshold dose of ghrelin (3ng/5 μl) did not affect the anorectic action of peripheral amylin. These results indicate that an interaction between central ghrelin and peripheral amylin on food intake seems unlikely, but cannot be ruled out completely. By contrast the lipostatic signals leptin and insulin may synergize with amylin in reducing food intake.