Normal glucose metabolism in carnivores overlaps with diabetes pathology in non-carnivores

Carnivores, such as the dolphin and the domestic cat, have numerous adaptations that befit consumption of diets with high protein and fat content, with little carbohydrate content. Consequently, nutrient metabolism in carnivorous species differs substantially from that of non-carnivores. Important metabolic pathways known to differ between carnivores and non-carnivores are implicated in the development of diabetes and insulin resistance in non-carnivores: (1) the hepatic glucokinase (GCK) pathway is absent in healthy carnivores yet GCK deficiency may result in diabetes in rodents and humans, (2) healthy dolphins and cats are prone to periods of fasting hyperglycemia and exhibit insulin resistance, both of which are risk factors for diabetes in non-carnivores. Similarly, carnivores develop naturally occurring diseases such as hemochromatosis, fatty liver, obesity, and diabetes that have strong parallels with the same disorders in humans. Understanding how evolution, environment, diet, and domestication may play a role with nutrient metabolism in the dolphin and cat may also be relevant to human diabetes

In vitro increase of mean corpuscular volume difference (dMCV) as a marker for serum hypertonicity in dogs.

Spurious increase in erythrocyte mean corpuscular volume (MCV) on automated cell analyzers is a well-characterized lab error in hypertonic patients. A difference between automated and manual MCV (dMCV) greater than 2 fl has been shown to predict hypertonicity in humans. The purpose of this study was to investigate dMCV as a marker for serum hypertonicity in dogs and to examine the relationship between dMCV and three methods of estimating serum tonicity: measured (OsM_M), calculated (OsM_C), and calculated effective (OsM_CE) osmolalities. OsM_C, OsM_CE, and dMCV were calculated from routine blood values and OsM_M was directly measured in 121 dogs. The dMCV of hypertonic dogs was significantly larger than that of normotonic dogs for all three osmolality methods. dMCV predicted hypertonicity as estimated by OsM_M better than it predicted hypertonicity as estimated by OsM_C and OsM_CE. A cutoff of 2.96 fl yielded the best sensitivity (76%) and specificity (71%) for hypertonicity estimated by OsMM

ATP-sensitive potassium channel (K(ATP )channel) expression in the normal canine pancreas and in canine insulinomas

BACKGROUND: Pancreatic beta cells express ATP-sensitive potassium (K(ATP)) channels that are needed for normal insulin secretion and are targets for drugs that modulate insulin secretion. The K(ATP )channel is composed of two subunits: a sulfonylurea receptor (SUR 1) and an inward rectifying potassium channel (Kir(6.2)). K(ATP )channel activity is influenced by the metabolic state of the cell and initiates the ionic events that precede insulin exocytosis. Although drugs that target the K(ATP )channel have the expected effects on insulin secretion in dogs, little is known about molecular aspects of this potassium channel. To learn more about canine beta cell K(ATP )channels, we studied K(ATP )channel expression by the normal canine pancreas and by insulin-secreting tumors of dogs. RESULTS: Pancreatic tissue from normal dogs and tumor tissue from three dogs with histologically-confirmed insulinomas was examined for expression of K(ATP )channel subunits (SUR1 and Kir(6.2)) using RT-PCR. Normal canine pancreas expressed SUR1 and Kir(6.2 )subunits of the K(ATP )channel. The partial nucleotide sequences for SUR1 and Kir(6.2 )obtained from the normal pancreas showed a high degree of homology to published sequences for other mammalian species. SUR1 and Kir(6.2 )expression was observed in each of the three canine insulinomas examined. Comparison of short sequences from insulinomas with those obtained from normal pancreas did not reveal any mutations in either SUR1 or Kir(6.2 )in any of the insulinomas. CONCLUSION: Canine pancreatic K(ATP )channels have the same subunit composition as those found in the endocrine pancreases of humans, rats, and mice, suggesting that the canine channel is regulated in a similar fashion as in other species. SUR1 and Kir(6.2 )expression was found in the three insulinomas examined indicating that unregulated insulin secretion by these tumors does not result from failure to express one or both K(ATP )channel subunits

Cloning and characterization of feline islet glucokinase

Background: Glucokinase (GK) is a metabolic enzyme encoded by the GCK gene and expressed in glucose-sensitive tissues, principally pancreatic islets cell and hepatocytes. The GK protein acts in pancreatic islets as a “glucose sensor” that couples fluctuations in the blood glucose concentration to changes in cellular function and insulin secretion. GCK and GK have proposed importance in the development and progression of diabetes mellitus and are potential therapeutic targets for diabetes treatment. The study was undertaken to determine the nucleotide sequence of feline pancreatic GK cDNA, predict the amino acid sequence and structure of the feline GK protein, and perform comparative bioinformatic analysis of feline cDNA and protein. Routine PCR techniques were used with cDNA from feline pancreas. Clones were assembled to obtain the full length cDNA. Protein prediction and modeling were performed using bioinformatic tools. Results: Full-length feline pancreatic GK cDNA contains a 1398 nucleotide coding sequence with high identity to other pancreatic GK cDNAs. The deduced 465 amino acid feline protein has 15 amino acid substitutions not found in other mammalian GK proteins but maintains high structural homology with human GK. Feline pancreatic GK is highly conserved at nucleotide and protein levels. Residues crucial for substrate binding and catalysis are completely conserved in the feline protein. Conclusion: Molecular analysis predicts that feline pancreatic GK functions similarly to other mammalian GK proteins

Midterm Outcomes and Aneurysm Sac Dynamics Following Fenestrated Endovascular Aneurysm Repair after Previous Endovascular Aneurysm Repair

Objective: Fenestrated endovascular aneurysm repair (FEVAR) is a feasible option for aortic repair after endovascular aneurysm repair (EVAR), due to improved peri-operative outcomes compared with open conversion. However, little is known regarding the durability of FEVAR as a treatment for failed EVAR. Since aneurysm sac evolution is an important marker for success after aneurysm repair, the aim of the study was to examine midterm outcomes and aneurysm sac dynamics of FEVAR after prior EVAR. Methods:Patients undergoing FEVAR for complex abdominal aortic aneurysms from 2008 to 2021 at two hospitals in The Netherlands were included. Patients were categorised into primary FEVAR and FEVAR after EVAR. Outcomes included five year mortality rate, one year aneurysm sac dynamics (regression, stable, expansion), sac dynamics over time, and five year aortic related procedures. Analyses were done using Kaplan–Meier methods, multivariable Cox regression analysis, chi square tests, and linear mixed effect models. Results: One hundred and ninety-six patients with FEVAR were identified, of whom 27% (n = 53) had had a prior EVAR. Patients with prior EVAR were significantly older (78 ± 6.7 years vs. 73 ± 5.9 years, p &lt; .001). There were no significant differences in mortality rate. FEVAR after EVAR was associated with a higher risk of aortic related procedures within five years (hazard ratio [HR] 2.6; 95% confidence interval [CI] 1.1 – 6.5, p = .037). Sac dynamics were assessed in 154 patients with available imaging. Patients with a prior EVAR showed lower rates of sac regression and higher rates of sac expansion at one year compared with primary FEVAR (sac expansion 48%, n = 21/44, vs. 8%, n = 9/110, p &lt; .001). Sac dynamics over time showed similar results, sac growth for FEVAR after EVAR, and sac shrinkage for primary FEVAR (p &lt; .001). Conclusion: There were high rates of sac expansion and a need for more secondary procedures in FEVAR after EVAR than primary FEVAR patients, although this did not affect midterm survival. Future studies will have to assess whether FEVAR after EVAR is a valid intervention, and the underlying process that drives aneurysm sac growth following successful FEVAR after EVAR.</p

Midterm Outcomes and Aneurysm Sac Dynamics Following Fenestrated Endovascular Aneurysm Repair after Previous Endovascular Aneurysm Repair

Objective: Fenestrated endovascular aneurysm repair (FEVAR) is a feasible option for aortic repair after endovascular aneurysm repair (EVAR), due to improved peri-operative outcomes compared with open conversion. However, little is known regarding the durability of FEVAR as a treatment for failed EVAR. Since aneurysm sac evolution is an important marker for success after aneurysm repair, the aim of the study was to examine midterm outcomes and aneurysm sac dynamics of FEVAR after prior EVAR. Methods:Patients undergoing FEVAR for complex abdominal aortic aneurysms from 2008 to 2021 at two hospitals in The Netherlands were included. Patients were categorised into primary FEVAR and FEVAR after EVAR. Outcomes included five year mortality rate, one year aneurysm sac dynamics (regression, stable, expansion), sac dynamics over time, and five year aortic related procedures. Analyses were done using Kaplan–Meier methods, multivariable Cox regression analysis, chi square tests, and linear mixed effect models. Results: One hundred and ninety-six patients with FEVAR were identified, of whom 27% (n = 53) had had a prior EVAR. Patients with prior EVAR were significantly older (78 ± 6.7 years vs. 73 ± 5.9 years, p &lt; .001). There were no significant differences in mortality rate. FEVAR after EVAR was associated with a higher risk of aortic related procedures within five years (hazard ratio [HR] 2.6; 95% confidence interval [CI] 1.1 – 6.5, p = .037). Sac dynamics were assessed in 154 patients with available imaging. Patients with a prior EVAR showed lower rates of sac regression and higher rates of sac expansion at one year compared with primary FEVAR (sac expansion 48%, n = 21/44, vs. 8%, n = 9/110, p &lt; .001). Sac dynamics over time showed similar results, sac growth for FEVAR after EVAR, and sac shrinkage for primary FEVAR (p &lt; .001). Conclusion: There were high rates of sac expansion and a need for more secondary procedures in FEVAR after EVAR than primary FEVAR patients, although this did not affect midterm survival. Future studies will have to assess whether FEVAR after EVAR is a valid intervention, and the underlying process that drives aneurysm sac growth following successful FEVAR after EVAR.</p

Agreeing language in veterinary endocrinology (ALIVE): diabetes mellitus - a modified Delphi-method-based system to create consensus disease definitions

[No abstract

Agreeing Language in Veterinary Endocrinology (ALIVE): Diabetes mellitus - a modified Delphi-method-based system to create consensus disease definitions

[No abstract