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1.
Sci Rep ; 8(1): 6109, 2018 04 17.
Article in English | MEDLINE | ID: mdl-29666448

ABSTRACT

Atmospheric new particle formation (NPF) and growth significantly influences the indirect aerosol-cloud effect within the polar climate system. In this work, the aerosol population is categorised via cluster analysis of aerosol number size distributions (9-915 nm, 65 bins) taken at Villum Research Station, Station Nord (VRS) in North Greenland during a 7 year record (2010-2016). Data are clustered at daily averaged resolution; in total, we classified six categories, five of which clearly describe the ultrafine aerosol population, one of which is linked to nucleation events (up to 39% during summer). Air mass trajectory analyses tie these frequent nucleation events to biogenic precursors released by open water and melting sea ice regions. NPF events in the studied regions seem not to be related to bird colonies from coastal zones. Our results show a negative correlation (r = -0.89) between NPF events and sea ice extent, suggesting the impact of ultrafine Arctic aerosols is likely to increase in the future, given the likely increased sea ice melting. Understanding the composition and the sources of Arctic aerosols requires further integrated studies with joint multi-component ocean-atmosphere observation and modelling.

2.
Sci Rep ; 8(1): 1482, 2018 01 24.
Article in English | MEDLINE | ID: mdl-29367716

ABSTRACT

The formation of new atmospheric particles involves an initial step forming stable clusters less than a nanometre in size (<~1 nm), followed by growth into quasi-stable aerosol particles a few nanometres (~1-10 nm) and larger (>~10 nm). Although at times, the same species can be responsible for both processes, it is thought that more generally each step comprises differing chemical contributors. Here, we present a novel analysis of measurements from a unique multi-station ground-based observing system which reveals new insights into continental-scale patterns associated with new particle formation. Statistical cluster analysis of this unique 2-year multi-station dataset comprising size distribution and chemical composition reveals that across Europe, there are different major seasonal trends depending on geographical location, concomitant with diversity in nucleating species while it seems that the growth phase is dominated by organic aerosol formation. The diversity and seasonality of these events requires an advanced observing system to elucidate the key processes and species driving particle formation, along with detecting continental scale changes in aerosol formation into the future.

3.
Physiol Behav ; 186: 79-81, 2018 03 15.
Article in English | MEDLINE | ID: mdl-29352965

ABSTRACT

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.


Subject(s)
Cats , Islets of Langerhans , Tissue Culture Techniques , Animals , Cell Survival , Islets of Langerhans/cytology , Islets of Langerhans/surgery , Male
4.
Sci Rep ; 7(1): 3318, 2017 06 12.
Article in English | MEDLINE | ID: mdl-28607400

ABSTRACT

Atmospheric new particle formation (NPF) and growth significantly influences climate by supplying new seeds for cloud condensation and brightness. Currently, there is a lack of understanding of whether and how marine biota emissions affect aerosol-cloud-climate interactions in the Arctic. Here, the aerosol population was categorised via cluster analysis of aerosol size distributions taken at Mt Zeppelin (Svalbard) during a 11 year record. The daily temporal occurrence of NPF events likely caused by nucleation in the polar marine boundary layer was quantified annually as 18%, with a peak of 51% during summer months. Air mass trajectory analysis and atmospheric nitrogen and sulphur tracers link these frequent nucleation events to biogenic precursors released by open water and melting sea ice regions. The occurrence of such events across a full decade was anti-correlated with sea ice extent. New particles originating from open water and open pack ice increased the cloud condensation nuclei concentration background by at least ca. 20%, supporting a marine biosphere-climate link through sea ice melt and low altitude clouds that may have contributed to accelerate Arctic warming. Our results prompt a better representation of biogenic aerosol sources in Arctic climate models.

5.
Vet Pathol ; 53(1): 136-44, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26113611

ABSTRACT

Pancreatic amyloidosis and loss of α and ß 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 ß 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 ß-cell loss.


Subject(s)
Amyloidosis/veterinary , Cat Diseases/pathology , Diabetes Mellitus/veterinary , Insulin/metabolism , Islets of Langerhans/pathology , Amyloidosis/metabolism , Amyloidosis/pathology , Animals , Cat Diseases/metabolism , Cats , Diabetes Mellitus/metabolism , Diabetes Mellitus/pathology , Female , Glucagon/metabolism , Islet Amyloid Polypeptide/metabolism , Islets of Langerhans/metabolism , Male , Pancreas/metabolism , Pancreas/pathology
6.
Vet Pathol ; 53(1): 145-52, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26319779

ABSTRACT

Pancreatitis has been described in cats with diabetes mellitus, although the number of studies currently available is very limited. In addition, ketoacidosis has been hypothesized to be associated with pancreatitis in diabetic cats. The aims of the present study were to investigate whether diabetic cats have pancreatitis and to determine if pancreatitis is more frequent with ketoacidosis. Samples of pancreas were collected postmortem from 37 diabetic cats, including 15 with ketoacidosis, and 20 control cats matched for age, sex, breed, and body weight. Sections were stained with hematoxylin and eosin, double-labeled for insulin/CD3, insulin/CD20, insulin/myeloperoxidase, insulin/PCNA, and glucagon/Ki67, and single-labeled for Iba1. A previously proposed semiquantitative score was used to characterize pancreatitis, along with counts of inflammatory cells. Scores of pancreatitis and the number of neutrophils, macrophages, and lymphocytes in the exocrine pancreas did not differ between diabetic and control cats or between diabetic cats with and without ketoacidosis. Of note, PCNA-positive acinar cells were increased (P = .002) in diabetic cats, particularly near islets (P < .001). Ki67-positive acinar cells were increased only near islets (P = .038). Ketoacidosis was not linked to proliferation. The results suggest that histopathologic evidence of pancreatitis may not be more frequent in diabetic cats and that ketoacidosis may not be associated with it at the time of death. Augmented PCNA-positive acinar cells might indicate increased proliferation due to chronic pancreatitis. The reason behind the prevalent proliferation of acinar cells surrounding pancreatic islets deserves further investigation.


Subject(s)
Cat Diseases/pathology , Diabetes Mellitus/veterinary , Ketosis/veterinary , Pancreas, Exocrine/pathology , Pancreatitis/veterinary , Acinar Cells/pathology , Animals , Cat Diseases/metabolism , Cats , Diabetes Mellitus/metabolism , Diabetes Mellitus/pathology , Female , Glucagon/metabolism , Insulin/metabolism , Ketosis/metabolism , Ketosis/pathology , Male , Pancreas/metabolism , Pancreas/pathology , Pancreas, Exocrine/metabolism , Pancreatitis/metabolism , Pancreatitis/pathology
7.
Environ Sci Technol ; 49(24): 13964-72, 2015 Dec 15.
Article in English | MEDLINE | ID: mdl-26529541

ABSTRACT

A number of field observations employing aerosol mass spectrometers (AMS) have demonstrated that organic matter rich in monocarboxylic acids and aliphatic carbonyls originating from cooking activities (the COA factor) contributes significantly to ambient organic matter (OM) in urban environments. Little is known about the contribution and nature of COA in rural localities. We studied the correlation of COA with chemical tracers at a rural site in the Po Valley, Italy. Our statistical approach, based on positive matrix factorization (PMF) shows that the COA factor was clearly linked to local emissions of chloride and methanesulfonic acid (MSA), chemical tracers not associated with cooking emissions, or with combustion sources. While the association with Cl is not understood at this stage, the emission of reduced sulfur compounds, aliphatic carbonyls and monocarboxylic acids is consistent with several agricultural practices (e.g., manure storage) and waste disposal systems (e.g., landfills) which characterize the suburban and rural areas of the Po Valley and of other many populated environments. It is concluded that the nature and origins of the AMS COA factor measured at a rural site are complex and include far more than the emissions from food cooking.


Subject(s)
Aerosols/analysis , Air Pollutants/analysis , Mass Spectrometry/methods , Agriculture , Air Pollutants/chemistry , Cooking , Italy , Manure , Mesylates/analysis , Refuse Disposal , Rural Population , Sulfur Compounds/analysis , Waste Disposal Facilities
8.
Environ Sci Pollut Res Int ; 21(20): 11649-60, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24385187

ABSTRACT

Water-soluble organic compounds (WSOCs), represented by anhydro-saccharides, dicarboxylic acids, and polyols, were analyzed by gas chromatography interfaced to mass spectrometry in extracts from 103 PM1 and 22 PM2.5 filter samples collected in an urban background and road site in Barcelona (Spain) and an urban background site in Los Angeles (USA), respectively, during 1-month intensive sampling campaigns in 2010. Both locations have similar Mediterranean climates, with relatively high solar radiation and frequent anti-cyclonic conditions, and are influenced by a complex mixture of emission sources. Multivariate curve resolution-alternating least squares analyses were applied on the database in order to resolve differences and similarities in WSOC compositions in the studied sites. Five consistent clusters for the analyzed compounds were obtained, representing primary regional biomass burning organic carbon, three secondary organic components (aged SOC, isoprene SOC, and α-pinene SOC), and a less clear component, called urban oxygenated organic carbon. This last component is probably influenced by in situ urban activities, such as food cooking and traffic emissions and oxidation processes.


Subject(s)
Aerosols/analysis , Cities , Organic Chemicals/analysis , Water/chemistry , Bicyclic Monoterpenes , Biomass , Butadienes/analysis , Hemiterpenes/analysis , Humans , Least-Squares Analysis , Los Angeles , Monoterpenes/analysis , Multivariate Analysis , Particulate Matter/analysis , Pentanes/analysis , Solubility , Spain , Time Factors
9.
Gen Comp Endocrinol ; 182: 48-53, 2013 Feb 01.
Article in English | MEDLINE | ID: mdl-23247272

ABSTRACT

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.


Subject(s)
Cat Diseases/metabolism , Cat Diseases/physiopathology , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/physiopathology , Animals , Cats , Humans , Insulin Resistance/physiology
10.
J Vet Intern Med ; 25(5): 1084-8, 2011.
Article in English | MEDLINE | ID: mdl-21985140

ABSTRACT

BACKGROUND: The continuous glucose monitoring system (CGMS) Guardian REAL-Time(®) 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.


Subject(s)
Blood Glucose/analysis , Cat Diseases/blood , Diabetes Mellitus/veterinary , Insulin/therapeutic use , Monitoring, Ambulatory/veterinary , Animals , Cat Diseases/drug therapy , Cats , Diabetes Mellitus/blood , Diabetes Mellitus/drug therapy , Female , Insulin/administration & dosage , Male , Monitoring, Ambulatory/instrumentation
11.
Endocrinology ; 152(3): 804-15, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21266508

ABSTRACT

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 ß-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.


Subject(s)
Adipose Tissue/physiopathology , Endotoxemia/metabolism , Inflammation/chemically induced , Lipid Metabolism/physiology , Lipoproteins/metabolism , Animals , Cats , Endotoxemia/chemically induced , Gene Expression Regulation , Insulin Resistance , Insulin-Secreting Cells , Lipopolysaccharides , Male
12.
Article in Spanish | IBECS | ID: ibc-84923

ABSTRACT

El objetivo de este artículo es concienciar a la Atención Primaria, Administraciones sanitarias, ayuntamientos y Asociaciones de Fibromialgia que, es posible desarrollar el Proceso Asistencial Integrado de Fibromialgia 2005 de la Consejería de Salud de Andalucía en el Distrito Sanitario Sevilla. Los recursos humanos y materiales, casi todos existen ya, solo habría que organizarlos. La Atención Primaria juega un importante papel como puerta de entrada (AU)


This article aims to raise awareness among Primary Care, Health Authorities, Municipalities and Fibromyalgia Associations that it is possible to implement the Fibromyalgia 2005 Integrated Health Process of the Andalusion Health Department in the Seville Health District. The human and material resources, already exist, and only have to be organised. Primary Care plays an important role as gateway to this process (AU)


Subject(s)
Humans , Male , Female , Primary Health Care/methods , Fibromyalgia/epidemiology , Fatigue Syndrome, Chronic/epidemiology , Medical Assistance/organization & administration , Social Work/methods , Social Work/trends , Primary Health Care/organization & administration , Primary Health Care , Fatigue Syndrome, Chronic/prevention & control , Public Assistance/organization & administration , Public Assistance/standards , Fibromyalgia/nursing
13.
J Vet Intern Med ; 24(6): 1314-21, 2010.
Article in English | MEDLINE | ID: mdl-20840299

ABSTRACT

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.


Subject(s)
Cat Diseases/pathology , Diabetes Mellitus/veterinary , Animals , Cats , Cohort Studies , Diabetes Mellitus/pathology , Female , Male , Remission, Spontaneous , Retrospective Studies
14.
Horm Metab Res ; 42(5): 340-7, 2010 May.
Article in English | MEDLINE | ID: mdl-20162504

ABSTRACT

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.


Subject(s)
Glucose/metabolism , Hyperlipidemias/metabolism , Inflammation/genetics , Insulin Resistance/genetics , Adipose Tissue/pathology , Animals , Bacteremia/blood , Blood Glucose/metabolism , Blotting, Western , Cats , DNA Primers , Fatty Acids, Nonesterified/blood , Glucose Tolerance Test , Glucose Transporter Type 4/metabolism , Hyperlipidemias/pathology , Insulin/blood , Liver/pathology , Male , PPAR gamma/metabolism , RNA/biosynthesis , RNA/genetics , Reverse Transcriptase Polymerase Chain Reaction , Triglycerides/blood
15.
J Vet Intern Med ; 24(1): 120-6, 2010.
Article in English | MEDLINE | ID: mdl-20002556

ABSTRACT

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.


Subject(s)
Blood Glucose/analysis , Cat Diseases/blood , Diabetes Mellitus/veterinary , Monitoring, Physiologic/veterinary , Animals , Cats , Diabetes Mellitus/blood , Female , Male , Monitoring, Physiologic/instrumentation , Sensitivity and Specificity
16.
Diabetologia ; 52(2): 336-46, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19034421

ABSTRACT

AIMS/HYPOTHESIS: 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. METHODS: We infused healthy cats with glucose or lipids for 10 days to clamp their blood concentrations at the approximate level found in untreated feline diabetes (glucose: 25-30 mmol/l; triacylglycerols: 3-7 mmol/l). RESULTS: Glucose and lipid levels were adequately targeted. Plasma non-esterified fatty acids were increased by lipid infusion 1.7-fold. A dramatic and progressive decline of plasma insulin levels was observed in glucose-infused cats beginning after 2 days of hyperglycaemic clamp. In contrast, plasma insulin concentration and glucose tolerance test were not affected by hyperlipidaemia. Compared with controls, glucose-infused cats had a 50% decrease in beta cells per pancreatic area. Apoptotic islet cells and cleaved caspase-3-positive beta cells were observed in glucose-infused cats only. CONCLUSIONS/INTERPRETATION: Sustained hyperglycaemia but not hyperlipidaemia induces early and severe beta cell dysfunction in cats, and excess glucose causes beta cell loss via apoptosis in vivo. Hyperglycaemic clamps in cats may provide a good model to study the pathogenesis of glucose toxicity in beta cells.


Subject(s)
Cat Diseases/physiopathology , Hyperglycemia/veterinary , Hyperlipidemias/veterinary , Insulin-Secreting Cells/physiology , Animals , Animals, Domestic , Blood Glucose/metabolism , Cats , Fatty Acids, Nonesterified/blood , Fatty Acids, Nonesterified/toxicity , Hyperglycemia/physiopathology , Hyperlipidemias/physiopathology , Insulin/blood , Insulin-Secreting Cells/metabolism , Insulin-Secreting Cells/pathology , Male
17.
Physiol Behav ; 91(5): 566-72, 2007 Aug 15.
Article in English | MEDLINE | ID: mdl-17481674

ABSTRACT

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 microl) reduced but did not completely reverse the intraperitoneal amylin (5 microg/kg)-induced inhibition of food intake. In comparison, administration of a sub-threshold dose of ghrelin (3 ng/5 microl) did not affect the anorexigenic action of peripheral amylin. Leptin administered into the third ventricle (i3vt; 3.5 microg/5 microl) and intraperitoneal amylin (5 microg/kg) synergistically reduced food intake in chow-fed rats. I3vt insulin, administered at a sub-threshold dose (0.5 mU/5 microl), 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.


Subject(s)
Amyloid/physiology , Appetite Regulation/physiology , Ghrelin/physiology , Insulin/physiology , Leptin/physiology , Satiation/physiology , Animals , Brain/physiology , Cross-Over Studies , Drug Synergism , Feeding Behavior/physiology , Ghrelin/administration & dosage , Injections, Intraventricular , Insulin/administration & dosage , Islet Amyloid Polypeptide , Leptin/administration & dosage , Male , Rats , Rats, Wistar
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