Insulin Sensitivity and β-Cell Function in Healthy Cats: Assessment with the Use of the Hyperglycemic Glucose Clamp

Abstract

A hyperglycemic clamp (HGC) was developed for use in conscious cats. In 21 healthy, normal glucose tolerant cats glucose disposal rate (M), insulin sensitivity (ISI_HGC), and β-cell response (I) at arterial plasma glucose of 9 mmol·l^-1 were measured. The HGC was tolerated well and steady state glucose infusion was achieved. Compared to values reported for humans, M values for the cats were low, which appeared to relate to both a low ISI_HGC and a low I. HGC measures correlated with fasting plasma glucose and insulin concentrations as well as with their HOMA (homeostasis model assessment) and QUICKI (quantitative insulin sensitivity check index) counterparts. Also, I and ISI_HGC correlated with their counterparts derived from intravenous glucose tolerance tests. In conclusion, this is the first report of hyperglycemic glucose clamping in cats. The procedure (HGC) allows for measurements of glucose disposal, β-cell response and insulin sensitivity. Compared to human data, both insulin sensitivity and insulin secretion appeared to be low in cats. This is compatible with the carnivorous nature of this species, for which insulin resistance would be advantageous during periods of restricted food availability.

Key words

diabetes mellitus - glucose tolerance test - HOMA - QUICKI - carnivore connection theory

References

• 1 Panciera DL, Thomas CB, Eicker SW, Atkins CE. Epizootiologic patterns of diabetes mellitus in cats: 333 cases (1980-1986).  J Am Vet Med Assoc. 1990;  197 1504-1508
• 2 O’Brien TD, Hayden DW, Johnson KH, Stevens JB. High dose intravenous glucose tolerance test and serum insulin and glucagon levels in diabetic and non-diabetic cats: relationships to insular amyloidosis.  Vet Pathol. 1985;  22 250-261
• 3 Feldhahn JR, Rand JS, Martin G. Insulin sensitivity in normal and diabetic cats.  J Feline Med Surg. 1999;  1 107-115
• 4 O’Brien TD. Pathogenesis of feline diabetes mellitus.  Mol Cell Endocrinol. 2002;  197 213-219
• 5 Stumvoll M, Goldstein BJ, van Haeften TW. Type 2 diabetes: principles of pathogenesis and therapy.  Lancet. 2005;  365 1333-1346
• 6 van Haeften TW. Early disturbances in insulin secretion in the development of type 2 diabetes mellitus.  Mol Cell Endocrinol. 2002;  197 197-204
• 7 Anonymous . Consensus Development Conference on Insulin Resistance. 5-6 November 1997. American Diabetes Association.  Diabetes Care. 1998;  21 310-314
• 8 Uwaifo GI, Fallon EM, Chin J, Elberg J, Parikh SJ, Yanovski JA. Indices of insulin action, disposal, and secretion derived from fasting samples and clamps in normal glucose-tolerant black and white children.  Diabetes Care. 2002;  25 2081-2087
• 9 Stumvoll M, Gerich J. Clinical features of insulin resistance and beta cell dysfunction and the relationship to type 2 diabetes.  Clin Lab Med. 2001;  21 31-51
• 10 Meneilly GS, Elliott T. Assessment of insulin sensitivity in older adults using the hyperglycemic clamp technique.  J Am Geriatr Soc. 1998;  46 88-91
• 11 Sowell MO, Mukhopadhyay N, Cavazzoni P, Shankar S, Steinberg HO, Breier A, Beasley Jr. CM, Dananberg J. Hyperglycemic clamp assessment of insulin secretory responses in normal subjects treated with olanzapine, risperidone, or placebo.  J Clin Endocrinol Metab. 2002;  87 2918-2923
• 12 Stumvoll M, Fritsche A, Haring H. The OGTT as test for beta cell function?.  Eur J Clin Invest. 2001;  31 380-381
• 13 Petrus DJ, Jackson MW, Kemnitz JW, Finegood DT, Panciera D. Assessing insulin sensitivity in the cat: evaluation of the hyperinsulinemic euglycemic clamp and the minimal model analysis.  Res Vet Sci. 1998;  65 179-181
• 14 Hasegawa S, Sako T, Koyama H, Motoyoshi S. Glucose utilization in cats, dogs and cows measured by euglycemic insulin clamp technique.  J Vet Med Sci. 1992;  54 583-584
• 15 Hoenig M, Thomaseth K, Brandao J, Waldron M, Ferguson DC. Assessment and mathematical modeling of glucose turnover and insulin sensitivity in lean and obese cats.  Domest Anim Endocrinol. 2006;  31 373-389
• 16 Xie H, Zhu L, Zhang YL, Legare DJ, Lautt WW. Insulin sensitivity tested with a modified euglycemic technique in cats and rats.  J Pharmacol Toxicol Methods. 1996;  35 77-82
• 17 Hsu WH, Hembrough FB. Intravenous glucose tolerance test in cats: influenced by acetylpromazine, ketamine, morphine, thiopental, and xylazine.  Am J Vet Res. 1982;  43 2060-2061
• 18 Bergman RN, Finegood DT, Ader M. Assessment of insulin sensitivity in vivo.  Endocr Rev. 1985;  6 45-86
• 19 Liu D, Moberg E, Kollind M, Lins PE, Adamson U, Macdonald IA. Arterial, arterialized venous, venous and capillary blood glucose measurements in normal man during hyperinsulinaemic euglycaemia and hypoglycaemia.  Diabetologia. 1992;  35 287-290
• 20 Speakman JR, Booles D, Butterwick R. Validation of dual energy X-ray absorptiometry (DXA) by comparison with chemical analysis of dogs and cats.  Int J Obes Relat Metab Disord. 2001;  25 439-447
• 21 Hoenig M, Alexander S, Holson J, Ferguson DC. Influence of glucose dosage on interpretation of intravenous glucose tolerance tests in lean and obese cats.  J Vet Intern Med. 2002;  16 529-532
• 22 DeFronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance.  Am J Physiol. 1979;  237 E214-E223
• 23 Elliott DA. Evaluation of multifrequency bioelectrical impedance analysis for the assessment of total body water and extracellular water in healthy cats and dogs. Thesis 2001 University of California-Davis, Davis
• 24 Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man.  Diabetologia. 1985;  28 412-419
• 25 Katz A, Nambi SS, Mather K, Baron AD, Follmann DA, Sullivan G, Quon MJ. Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans.  J Clin Endocrinol Metab. 2000;  85 2402-2410
• 26 Grubbs FE. Procedures for detecting outlying observations in samples.  Technometrics. 1969;  11 1-21
• 27 Lilliefors HW. On the Kolmogorov-Smirnov test for normality with mean and variance unknown.  J Am Stat Assoc. 1967;  62 399-402
• 28 Link KRJ, Rand JS. Reference values for glucose tolerance and glucose tolerance status in cats.  J Am Vet Med Assoc. 1998;  213 492-496
• 29 Goodger WJ. Clinical management of intra-arterial catheters for blood pressure determinations and blood gas analysis.  J Am Anim Hosp Assoc. 1972;  8 428-431
• 30 Thuranszky K. Continuous blood pressure measurement in non-anaesthetized animals.  Acta Physiol Acad Sci Hung. 1966;  29 33-39
• 31 Kruth SA, Cowgill LD. Renal glucose transport in the cats. Proceedings of the Scientific meeting of the American College of Veterinary Internal Medicine, Salt Lake City.  1982;  29
• 32 Chan SS, Lotspeich WD. Comparative effects of phlorizin and phloretin on glucose transport in the cat kidney.  Am J Physiol. 1962;  203 975-979
• 33 Kashyap S, Belfort R, Gastaldelli A, Pratipanawatr T, Berria R, Pratipanawatr W, Bajaj M, Mandarino L, DeFronzo R, Cusi K. A sustained increase in plasma free fatty acids impairs insulin secretion in nondiabetic subjects genetically predisposed to develop type 2 diabetes.  Diabetes. 2003;  52 2461-2474
• 34 Mitrakou A, Vuorinen-Markkola H, Raptis G, Toft I, Mokan M, Strumph P, Pimenta W, Veneman T, Jenssen T, Bolli G. Simultaneous assessment of insulin secretion and insulin sensitivity using a hyperglycemia clamp.  J Clin Endocrinol Metab. 1992;  75 379-382
• 35 van Haeften TW, Pimenta W, Mitrakou A, Korytkowski M, Jenssen T, Yki-Jarvinen H, Gerich JE. Relative contributions of β-cell function and tissue insulin sensitivity to fasting and postglucose-load glycemia.  Metabolism. 2000;  49 1318-1325
• 36 Bevilacqua S, Barrett EJ, Smith D, Simonson DC, Olsson M, Bratusch-Marrain P, Ferrannini E, DeFronzo RA. Hepatic and peripheral insulin resistance following streptozotocin-induced insulin deficiency in the dog.  Metabolism. 1985;  34 817-825
• 37 Clark PM. Assays for insulin, proinsulin(s) and C-peptide.  Ann Clin Biochem. 1999;  36 541-564
• 38 Bergman RN. Lilly lecture 1989. Toward physiological understanding of glucose tolerance. Minimal-model approach.  Diabetes. 1989;  38 1512-1527
• 39 Ferris WF, Naran NH, Crowther NJ, Rheeder P, van der Merwe L, Chetty N. The relationship between insulin sensitivity and serum adiponectin levels in three population groups.  Horm Metab Res. 2005;  37 695-701
• 40 Chang JC, Wu MC, Liu IM, Cheng JT. Increase of insulin sensitivity by stevioside in fructose-rich chow-fed rats.  Horm Metab Res. 2005;  37 610-616

Correspondence