Planta Med 2002; 68(7): 581-590
DOI: 10.1055/s-2002-32894
Review
© Georg Thieme Verlag Stuttgart · New York

Recommended Testing in Diabetes Research

E. J. Verspohl1
  • 1Dept. of Pharmacology, Institute of Pharmaceutical and Medicinal Chemistry, Münster, Germany
Further Information

Publication History

Received: July 6, 2001

Accepted: January 20, 2002

Publication Date:
22 July 2002 (online)

Abstract

Diabetic disease is increasing rapidly and vast amounts of resources are spent in all countries. Thus, the screening of new compounds including plant extracts for antidiabetic effects is mandatory. In this review both simple assays [e.g., on blood glucose (after or without a glucose load), plasma insulin and extrapancreatic effects] are described as well as specific in vivo tests in diabetic animals and in vitro tests with respect to the mechanism of compounds. In total, approx. 30 selected tests are evaluated and references are given. Thus, the investigator is guided through the tests and is advised that measuring only one parameter such as glucose will not be sufficient. In the case that the financial resources are poor for the investigator, more than glucose still has to be measured. A balance is made by describing absolutely necessary investigations while concentrating on those at low cost. It has to be started with simple assays; to use one test only, however, means oversimplifying the diabetes disease; additionally antidiabetic effects may be missing. The investigator is guided through the advantages and limitations of diabetic animal models and is advised about specific in vitro tests to look at the mechanism of action. All investigators should profit from these details, not only the phytoresearchers.

References

  • 1 Hauner H. Verbreitung des Diabetes mellitus in Deutschland.  Dtsch. Med. Wschr.. 1998;  123 777-82
  • 2 Sohda T, Momose Y, Meguro K, Kawamatsu Y, Sugiyama Y, Ikeda H. Studies on antidiabetic agents. Synthesis and hypoglycemic activity of 5-[4-(pyridylalkoxy)benzyl]-2,4-thiazolidineodiones.  Arzneim. Forschg./Drug Res.. 1990;  40 37-42
  • 3 Bailey C J, Turner S L, Jakeman K J, Hayes W A. Effect of Coprinus comatus on plasma glucose concentrations in mice.  Planta Med.. 1984;  50 525-6
  • 4 Starr J I. In: Jaffe BM, Behrmann HR (eds) Methods of Hormone Radioimmunoassay; 2nd ed. Academic press New York; 1979: pp. 613-42
  • 5 Verspohl E J, Ammon H PT. Evidence for presence of insulin receptors in rat islets of Langerhans.  J. Clin. Invest.. 1980;  65 1230-7
  • 6 Grodsky G M, Heldt A. Method for the in vitro perfusion of the pancreas. In: Larner J, Pohl SL (eds) Methods in Diabetes Research. Vol. I Laboratory Methods. Part B John Wiley & Sons New York; 1984: 137-46
  • 7 Chick W L, Warren S, Chute R N, Like A A, Lauris V, Kitchen K C. A transplantable insulinoma in the rat.  PNAS. 1977;  74 628-32
  • 8 Kraegen E W, James D E, Jenkins A B, Chisholm D J. Dose-response curves for in vivo sensitivity in individual tissues in rats.  Am. J. Physiol.. 1985;  11 E353-62
  • 9 Like A A, Rossini A A. Streptozotocin-induced pancreatic insulitis: A new model of diabetes mellitus.  Science. 1976;  133 415-7
  • 10 Frerichs H, Creutzfeldt W. Diabetes durch Beta-Zytotoxine. In: Pfeiffer EF (ed.) Handbook of Diabetes mellitus, Pathophysiology and Clinical Considerations. Vol. I, Lehmanns Verlag München; 1968: pp. 811-40
  • 11 Goto Y, Suzuki K, Ono T, Sasaki M, Toyota T. Development of diabetes in the non-obese NIDDM rat (GK rat).  Adv. Exp. Med. Biol.. 1988;  246 29-31
  • 12 Herberg L, Coleman D L. Laboratory animals exhibiting obesity and diabetes syndromes.  Metabolism. 1977;  26 59-99
  • 13 Koletsky S. Pathologic findings and laboratory data in a new strain of obese hypertensive rats.  Am. J. Pathol.. 1975;  80 129-42
  • 14 McCaleb M L, Sredy J. Metabolic abnormalities of the hyperglycemic obese Zucker rat.  Metabolism. 1992;  41 522-5
  • 15 Zucker L M. Hereditary obesity in the rat associated with hyperlipidemia.  Ann. NY Acad. Sci.. 1965;  131 447-58
  • 16 Coleman D L, Hummel K P. Studies with the mutation diabetes in the mouse.  Diabetologia. 1967;  3 238-48
  • 17 Fujiwara T, Yoshioka S, Yoshioka T, Ushiyama I, Horikoshi H. Characterization of new oral antidiabetic agent CS-045. Studies in KK and ob/ob mice and Zucker fatty rats.  Diabetes. 1988;  37 1549-58
  • 18 Shafir E. Animal models of non-insulin dependent diabetes.  Diabetes/Metab. Rev.. 1992;  8 179-208
  • 19 Nakhooda A F, Like A A, Chappel C I, Wie C N, Marliss E B. The spontaneous diabetic Wistar rat (the “BB” rat). Studies prior to and during development of the overt syndrome.  Diabetologia. 1978;  14 199-207
  • 20 Tochino Y. Breeding and characteristics of a spontaneously diabetic non obese strain (NOD mouse) of mice. In: Shafrir E, Renold AE (eds) Lessons from Animal Diabetes;. John Libbey London; 1984: pp. 93-8
  • 21 Lenzen S, Tiedge M, Elsner M, Lortz S, Weiss H, Jörns A, Klöppel G, Wedekind D, Prokop C-M, Hedrich H J. The LEW.1AR1/Ztm-iddm rat: a new model of spontaneous insulin-dependent diabetes mellitus.  Diabetologia. 2001;  44 1189-96
  • 22 Marquie G, Duhault J, Jacotot B. Diabetes mellitus in sand rats (Psammomys obesus). Metabolic pattern during development of the diabetic syndrome.  Diabetes. 1984;  33 438-43
  • 23 Pictet R, Orci L, Gonet A E, Rouiller Ch, Renold A E. Ultrastructural studies of the hyperplastic islets of Langerhans of spiny mice (Acomys cahirnus).  Diabetologia. 1967;  3 188-211
  • 24 Wise P H, Wier B J, Hime J M, Forrest E. The diabetic syndrome in the Tuco-Tuco (Ctenomis talarum).  Diabetologia. 1972;  8 165-72
  • 25 Foley J E, Gliemann J. Accumulation of 2-deoxyglucose against its concentration gradient in rat adipocytes.  Biochim. Biophys. Acta. 1981;  648 100-6
  • 26 Garvey W T, Hardin D, Juhaszova M, Dominguez J H. Effects of diabetes on myocardial glucose transport system in rats: implications for diabetic cardiomyopathy.  Am. J. Physiol.. 1993;  264 H837-44
  • 27 Marette A, Bukowiecki L J. Stimulation of glucose transport by insulin and norepinephrine in isolated rat brown adipocytes.  Am. J. Physiol. . 1989;  257 C714-21
  • 28 Basi N S, Thomaskutti K G, Pointer R H. Regulation of glucose transport in isolated adipocytes by levomisole.  Can J Physiol Pharmacol. 1992;  70 1190-4
  • 29 Prip-Buus C, Bouthillier-Voisin A C, Kohl C, Demaugre F, Girard J, Pegorier J P. Evidence for an impaired long-chain fatty acid oxidation and ketogenesis in Fao hepatoma cells.  Eur. J. Biochem.. 1992;  209 291-8
  • 30 Busshardt E, Gerok W, Haussinger D. Regulation of hepatic parenchymal and non-parenchymal cell function by the diadenine nucleotides Ap3A and Ap4A.  Biochim. Biophys. A.. 1989;  1010 151-9
  • 31 Smith R L, Lawrence J C. Insulin action in denervated rat hemidiaphragm.  J. Biol. Chem.. 1984;  259 2201-7
  • 32 Oron Y, Larner J. A modified rapid filtration assay of glycogen synthase.  Anal. Biochem.. 1979;  94 409-10
  • 33 Mühlbacher C, Karnieli E, Schaff P, Obermaier B, Mushack J, Rattenhuber E, Häring H U. Phorbol esters initiate in rat fat cells the full effect of insulin on glucose-carrier translocation, but not on 3-O-methylglucose transport activity.  Biochem. J.. 1989;  249 865-70
  • 34 Brozinick J T, Etgen G J. The effects of muscle contraction and insulin on glucose transporter translocation in rat skeletal muscle.  Biochem. J.. 1994;  297 539-45
  • 35 Müller G, Wied S. The sulfonylurea drug, glimepiride, stimulates glucose transport, glucose transporter translocation, and dephosphorylation in insulin-resistant rat adipocytes in vitro .  Diabetes. 1993;  42 1852-67
  • 36 Vila M DC, Milligan G, Standaert M L, Farese R V. Insulin activates glycerol-3-phosphate-acyltransferase (de novo phosphatidic acid synthesis) through a phospholipid-derived mediator. Apparent involvement of G and activation of a phospholipase C.  Biochem.. 1990;  29 8735-40
  • 37 Koch R, Weber U. Partial purification of the solubilized insulin receptor from rat liver membranes by precipitation with concanavalin A. H-S.  Z. Physiol. Chem.. 1981;  362 347-51
  • 38 Ashcroft S JH, Ashcroft F M. The sulfonylurea receptor.  Biochim. Biophys. Acta. 1992;  1175 45-59
  • 39 Nicki I, Nicks J L, Ashcroft S JH. The β-cell gilbenclamide receptor is an ADP-binding protein.  Biochem. J.. 1990;  268 713-8
  • 40 Colca J R. Insulin sensitizer drugs in development for the treatment in diabetes.  Expert. Opin. Invest. Drugs. 1995;  4 27-9
  • 41 Maeda N, Takahashi M, Funahashi T, Kihura S, Nishizawa H, Kishida K, Nagaretani H, Matsuda M, Komuro R, Ouchi N, Kuriyama L, Hotta K, Nakamura T, Shinomura I, Matsuzawa Y. PPARgamma ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein.  Diabetes. 2001;  50 2094-9
  • 42 Matsuo T, Odaka H, Ikeda H. Effect of an intestinal disaccharidase inhibitor (AO-128) on obesity and diabetes.  Am. J. Clin. Nutr.. 1992;  55: Suppl 1 314S-317S
  • 43 Madar Z, Omusky Z. Inhibition of intestinal α-glucosidase activity and postprandial hyperglycemia by α-glucosidase inhibitors in fa/fa rats.  Nutr. Res.. 1991;  11 1035-46
  • 44 Terashima H, Hama K, Yamamoto R, Tsuboshima M, Kikawa R, Hatanaka I, Shigeta Y. Effects of a new aldose reductase inhibitor on various tissues in vitro .  J. Pharmacol. Exp. Ther.. 1984;  229 226-30
  • 45 British Pharmacopoeia. 1988 Vol II
  • 46 Verspohl E J, Roth R A, Vigneri R, Goldfine I D. Dual regulation of glycogen metaoblism by insulin and IGF-I in human hepatoma cells (HEP-G2): Analysis with an antireceptor monoclonal antibody.  J. Clin. Investig.. 1984;  74 1436-43
  • 47 Geisen K. Special pharmacology of the new sulfonylurea glimepiride.  Arzneim. Forschg./Drug Res.. 1988;  38 1120-30
  • 48 Wieland O. Glycerin UV-Methode. In: Bergmeyer HU (ed) Methoden der enzymatischen Analyse. Verlag Chemie Weinheim; 1974: pp. 1448-53
  • 49 Zhang Zhang B, Salituro G, Szalkowski D, Li Z, Zhang Y, Royo I, Vilella D, Diez M T, Pelaez F, Ruby C, Kendall R L, Mao X, Griffin P, Calaycay J, Zierath J R, Heck J V, Smith R G, Moller D E. Discovery of a small molecule insulin mimetic with antidiabetic activity in mice.  Science. 1999;  284 974-7

General Literature/Reviews:

Joost H-G, Herberg L. Krankheitsmodelle in der Arzneimittelforschung (Vorträge vor der Paul-Martini-Stiftung). Arzneim. Forschg./Drug Research Suppl. 1998

McNeill JH. Experimental Models of diabetes. CRC Press, LLC, 1999

Terashima H, Hama K, Yamamoto R, Tsuboshima M, Kikkawa R, Hatanaka I, Shigeta Y. Effects of a new aldose reductase inhibitor on various tissues in vitro. J. Pharmacol. Exp. Ther. 1984; 229: 226 - 30

Vogel HG, Vogel WH. Drug Discovery and Evaluation. Springer Verlag, Berlin, Heidelberg, New York, pp. 535 - 97

E. J. Verspohl

Dept. of Pharmacology

Institute of Pharmaceutical and Medicinal Chemistry

Hittorfstr. 58 - 62

48149 Münster

Germany

Phone: +49-251-8333339

Fax: +49-251-8332144

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