Hitomi ODA

Ezetimibe is a cholesterol absorption inhibitor that blocks the intestinal absorption of both biliary and dietary cholesterol, thereby lowering primarily low density lipoprotein-cholesterol (LDL-chol) in human studies. This study aimed to investigate the effects of ezetimibe on dyslipidemia control in nine dogs with hypercholesterolemia. Changes in total cholesterol (T-chol) and each lipoprotein fractions were evaluated at 0, 2, and 4 months following initiation of ezetimibe treatment. A significant decrease in T-chol was observed, and a mean T-chol concentration below 400 mg/dL was achieved at 2 and 4 months. Furthermore, a significant decrease in LDL-chol was observed (-53.3% and -64.3% at 2 and 4 months, respectively). Taken together, treatment of ezetimibe could lower LDL-chol levels in dogs with hypercholesterolemia.

Insulin degludec (IDeg) is a long-acting basal insulin recently developed for use in humans. This study aimed to investigate the effects of IDeg on glycemic control in diabetic cats. Changes in body weight, IDeg dosage, and glycated albumin (GA) were evaluated at 0, 1, 3, 6, 9, and 12 months following initiation of IDeg. A significant decrease in GA was observed and a mean GA level below 25% was achieved between 3 and 12 months. Furthermore, a significant increase in body weight was observed between 3 and 12 months. The mean IDeg dose was 0.75 ± 0.68 IU/kg/day at 12 months. Taken together, long-term glycemic control was successfully achieved in diabetic cats using IDeg.

ヒトの医学領域および多くの哺乳動物において、食事中の栄養素(特に炭水化物と脂肪)がグルコース依存性インスリン分泌刺激ポリペプチド(GIP)やグルカゴン様ペプチド-1(GLP-1)といったインクレチン分泌を促進することが知られている。さらにヒトでは2つの異なる脂肪源(飽和脂肪酸を多く含むラードと不飽和脂肪酸を多く含む大豆油)によってインクレチンの分泌量が変化することが報告された。本研究では、食事中の異なる脂肪源(ラードおよび大豆油)が健常猫のGIP、GLP-1分泌、そして血糖値、インスリン、中性脂肪、NEFAにどのような影響を及ぼすのかを検討した。低脂肪食であるbasal食と、ラードと大豆油の2種の脂肪をbasal食に加えた高脂肪食を、それぞれ14日間ずつ給与した。結果として高脂肪食給与下ではGIP分泌とNEFA濃度が有意に上昇した。しかし、GLP-1分泌および血糖値やインスリン、TG濃度に有意差は認められなかった。また、異なる脂肪源は猫のGIP分泌に大きな影響は与えない可能性が示唆された。(著者抄録)

Insulin degludec (IDeg) is a new insulin formulation that facilitates long-term control of glucose level in humans. In this study, we investigated the effects of IDeg on glycemic control in dogs. Its time-action profiles were monitored in healthy dogs using an artificial pancreas apparatus under euglycemic conditions. At 9.0-13.5 hr post-IDeg injection, an indistinct peak of glucose level was detected. Moreover, the action of IDeg was persistent for >20 hr. Both IDeg and neutral protamine Hagedorn insulin (NPH) lowered blood glucose concentrations in diabetic dogs, but IDeg caused postprandial hyperglycemia and a somewhat lower preprandial glucose level than that caused by NPH. IDeg might be ineffective in concurrently preventing postprandial hyperglycemia and preprandial hypoglycemia in a single-agent administration.

<p><tt>In the diabetes cats, infectious diseases such as urinary tract infection and periodontal disease are frequently observed accompanying depression immunocompetence. Cats are more likely susceptible to stress-induced hyperglycemia and limited in hypoglycemic activity. Therefore, it is often very difficult to maintain glycemic control such as diabetes mellitus（DM）cats with these problems. This study used 3 cases of DM patient of our university teaching hospital. These cats have been suffered from chronic inflammations, and poorly-glycemic control due to stress. In order to achieve these objectives, we need to make good use of the learnings from each case and problems with hospitalized animals. We can give appropriate advice to care in their home after discharge. Moreover we need to consider each cat preference and stress inducers when we take care of hospitalized patients, and vet nurses provide them with comfortable environment as much as possible by increasing their satisfactio</tt><tt>n level and eliminating in hospitals. </tt></p>

Anion-exchange (AEX)-high-performance liquid chromatography (HPLC) for measurement of cholesterol can be used to separate serum lipoproteins (high-density lipoprotein (HDL); low-density lipoprotein (LDL); intermediate-density lipoprotein (IDL); very-low-density lipoprotein (VLDL)) in humans. However, AEX-HPLC has not been applied in veterinary practice. We had three objectives: (i) the validation of AEX-HPLC methods including the correlation of serum cholesterol concentration in lipoprotein fraction measured by AEX-HPLC and gel permeation-HPLC (GP-HPLC) in healthy dogs and those with hypercholesterolemia was investigated; (ii) the reference intervals of lipoprotein fractions measured by AEX-HPLC from healthy dogs (n = 40) was established; (iii) lipoprotein fractions from the serum of healthy dogs (n = 12) and dogs with hypercholesterolemia (n = 23) were compared. Analytic reproducibility and precision of AEX-HPLC were acceptable. Positive correlation between serum concentrations of total cholesterol (Total-Chol), HDL cholesterol (HDL-Chol), LDL cholesterol (LDL-Chol) + IDL cholesterol (IDL-Chol), and VLDL cholesterol (VLDL-Chol) was noted for AEX-HPLC and GP-HPLC in healthy dogs and dogs with hypercholesterolemia. Reference intervals measured by AEX-HPLC for serum concentrations of Total-Chol, HDL-Chol, and LDL-Chol were determined to be 2.97-9.32, 2.79-6.57, 0.16-3.28 mmol/L (2.5-97.5% interval), respectively. Furthermore, there was significant difference in lipoprotein profiles between healthy and dogs with hypercholesterolemia. These results suggest that AEX-HPLC can be used to evaluate lipoprotein profiles in dogs and could be a new useful indicator of hyperlipidemia in dogs.

<p>Incretins such as glucose-dependent insulinotropic peptide（GIP）and glucagon like peptide-1（GLP-1）were shown to exert their insulinotropic effects through a variety of mechanisms. In the presence of matched glucose concentrations, insulin secretion is greater following ingestion of glucose than following infusion of glucose. This was referred to as "the incretin effect"and GIP and GLP-1 are released by gut endocrine cells in response to a meal and regulate blood glucose levels by stimulating glucose-dependent insulin secretion. The purpose of this study was to investigate the effect of incretin secretion for glucose and insulin metabolism in healthy cats. In order to determine changes in incretin secretion with different nutritional composition （control, high-carbohydrate, high-fat, high-fiber）, different diets were fed in 5 healthy cats. We measured postprandial glucose, insulin, GIP and GLP-1 concentrations. No significant changes in mean glucose and insulin concentrations. Furthermore, GLP-1 concentration was not significantly difference in 4 type diets. Meanwhile, GIP secretion was increased in high-fat diet. Furthermore, GIP was increased in direct proportion to fat content of these diets. As the result of GIP secretion was increased in high- fat diet, similarly as with humans and rodents. However, GLP-1 was not consistent with human objects, and we suggest that cats have been different digestive tissue and feeding habit.</p>

This study investigated the changes in lymphocyte subsets during the trilostane medication of Pituitary-dependent hyperadrenocorticism (PDH) dogs. The cortisol level and lymphocyte subsets of eight dogs with PDH were monitored 0, 1, 3, 6, 9 and 12 months after the initiation of trilostane treatment. White blood cells (WBC), lymphocytes, CD3(+) (T lymphocyte), CD4(+) (helper T lymphocyte), CD8(+) (cytotoxic T lymphocyte) and CD21(+) (B lymphocyte) cells were measured. Although the post-ACTH stimulation test cortisol level was significantly lower during trilostane treatment, changes in the CD3(+), CD4(+), CD8(+) and CD21(+) counts were not observed. Meanwhile, significant decrease was observed in WBC counts during trilostane treatment. These indicate that long-term trilostane treatment has little effect on the lymphocyte subsets in PDH dogs.

Sitagliptin is a dipeptidyl peptidase-4 inhibitor aimed at treating Type 2 diabetes mellitus (T2DM) and T1DM, by increasing blood levels of Glucagon-like peptide 1 (GLP-1) and insulin. The objective of this preliminary study is to characterize Sitagliptin's ability for glycemic control, in healthy dogs under an oral glucose tolerance test (OGTT) environment. Overall, Sitagliptin did not result in any significant changes to temporal glucose and insulin concentrations. However, a similar to 55% increase in median total GLP-1 AUC(0-120min) was observed, as compared to baseline control in healthy dogs (n=5), thus indicating a similar mode of action of Sitagliptin between healthy dogs and humans. Future studies to validate the use of Sitagliptin with dogs suffering from insulin independent diabetes are warranted.

Glucagon-like peptide 1 (GLP-1) is a glucose-lowering, intestinal-derived factor with multiple physiological effects, making it attractive for diabetes therapy. However, the therapeutic potential of endogenous GLP-1 is limited, because of rapid inactivation by dipeptidyl peptidase-4. Recently, enhanced incretin preparations, such as liraglutide, have emerged, which are more resistant to degradation and longer lasting. Liraglutide is a long-acting acylated human GLP-1 receptor agonist, with a 97% amino acid sequence identity to endogenous human GLP-1, and 100% amino acid sequence homology with canine GLP-1.Since liraglutide has yet to be examined for use in dogs, and the incretin effect has been reported to exist in dogs, we sought to initially characterize liraglutide's ability for glycemic control in healthy dogs, under an oral glucose tolerance test (OGTT) environment initially. This was followed up a more realistic scenario involving food with insulin injection +/- liraglutide injection resulting in a glucose curve based study involving dogs suffering from Type 1 diabetes mellitus (T1DM). Overall, liraglutide had a stabilizing effect on glucose levels, maintaining circulating levels between 77.0 and 137.0mg/ml throughout the OGTT test period, resulting in a significant reduction of 13.8% in glucose AUC0-120min (total area under the curve for 0-120min) as compared to baseline control in healthy dogs (n=5). Interestingly, the liraglutide associated reduction in circulating glucose was not accompanied by any significant increase in insulin. Moreover, T1DM dogs (n=4) responded favorably to liraglutide treatment, which lead to a significant reduction of 46.0% in glucose AUC0-12h (total area under the curve for 0-12h), and a significant reduction of 66.5% in serum glucose as compared to baseline controls (insulin treatment only). Therefore, liraglutide's prandial glucagon suppressive ability appears to play a key role in its glucose-lowering capability, and offers great potential for use with dogs suffering from T1DM. © 2013 Elsevier Ltd.

Diabetes mellitus (DM) is one of the risk factors for periodontitis. Periodontal treatment improved glycemic control in diabetic human patients. Furthermore, it had been noticed that oxidant stress was increased in diabetic patients with periodontal diseases. The purpose of this study is to evaluate whether periodontal treatment effect for glycemic control and oxidant stress level in dogs with DM. Four dogs with DM maintained in our laboratory were used in this study. All diabetic dogs had chronic periodontitis, gingivitis and dental calculus. We evaluated glycated albumin (GA) and fasting blood glucose concentration (FBG) as glycemic control markers, and evaluated C-reactive protein (CRP) and tumor necrosis factor alpha (TNF-&amp;alpha;) as inflammation markers, and evaluated d-ROMs (reactive oxygen metabolites) and BAP ( biological antioxidant potential) levels as oxidant stress markers before and after the periodontal treatment. Results indicated significant decrease in GA and CRP levels after periodontal treatment. Furthermore, a significant increase was observed in BAP level. However, there was no significant difference in FBG and TNF-&amp;alpha; concentration and d-ROM level. These results suggested that periodontal treatment could improve glycemic control in dogs with DM.