小田 民美

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>糖尿病猫はしばしば感染症に罹患しやすいといわれており、またストレス性の高血糖を生じやすく、血糖値を降下させるのも不得手な動物種である。このような特性をもつ猫の糖尿病管理においては、血糖コントロールを悪化させる原因が数々存在するため、糖尿病猫の入院管理は時に困難をともなう。そこで本学に来院した、慢性感染症を併発した猫、入院によるストレスで血糖コントロールが困難となった猫、食事変更が必要となった猫について、その問題と対策について検討した。症例によってストレスを感じる事象は様々あり、その対処も大きく異なるものであった。同時に、院内で起こる特有の問題からの学びもあり、退院後の自宅でのケアに生かすことができた。病院という制限ある集団管理においても、可能な限りその個別性を大切に、それぞれに合った生活環境を整える工夫ができるかが動物看護師の重要な仕事であると考える。</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>GLP-1およびGIPは共に血糖依存的にインスリンを分泌させる他、様々な臓器で多様な作用を持ち糖代謝に深く関与している消化管ホルモンである。本研究では栄養組成の違いがネコのインクレチン分泌におよぼす影響について検討することを目的とした。日本獣医生命科学大学で飼育管理されている健常猫5頭に、コントロール食、高炭水化物食、高脂肪食、高繊維食の4種を給与し、血糖値、インスリン濃度およびインクレチン濃度を測定した。GLP-1濃度変動は4種の食事で差はなかった。この結果は、ヒトでは炭水化物と脂質がGLP-1分泌に大きく影響をおよぼしているという報告とは異なるものであった。これはネコの食性や消化管構造の違いによる影響と考えられた。一方、GIP濃度変動はコントロール食と比較し高脂肪食で有意に高値を示した。また、食事中の脂肪含量が多いほどGIP濃度も高値を示した。本研究により、ネコにおいて栄養組成の違いがGIP分泌におよぼす影響について明らかとなったが、GLP-1分泌については今後さらなる検討が必要である。</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.

糖尿病犬はしばしば尿路感染症や歯周病などの感染症に羅患しやすいことが知られている。またヒトの糖尿病患者において、歯周病は血糖コントロールを悪化させるという報告が数々ある。本研究では糖尿病犬に歯科処置を行い、血糖コントロールにどのような影響を及ぼすかを検討した。本学で飼育している糖尿病犬4頭を用いた。血液サンプリングは歯科処置前と歯科処置1、2、3、4週間後に行った。測定項目は、空腹時血糖値 (FBG) と長期血糖コントロールマーカーとして用いられる糖化アルブミン (GA) を測定した。また、炎症マーカーとして腫瘍壊死因子-&amp;alpha; (TNF-&amp;alpha;) 、CRP、生体内酸化ストレスマーカーとして酸化ストレス度を示すd-ROM、抗酸化力を示すBAPを測定した。GAとCRPは歯科処置前に比べ4週間後で有意に低下した。しかし、FBG、TNF-&amp;alpha;には処置前後で有意な変化は認められなかった。d-ROMは処置前後で有意な変化は認められなかったが、BAPは処置前に比べ処置後4週間で有意に上昇していた。以上より、歯科処置が口腔内炎症を抑制し、血糖コントロールを良化させたと考えられる。さらに、炎症の抑制や血糖コントロールの改善が、生体内における抗酸化力を増加させたことが示唆された。