Kurt S. Zänker, MD, DVM, PhD.,

Professor of Immunology & Exp. Oncology,

KSZ@uni-wh.de

Momordica charantia for type 2 diabetes:

A randomized, placebo-controlled, double-blinded and

prospective clinical study as add-on combination to

ongoing oral anti-diabetes therapies.

Epidemiology

Metabolic Syndrome:

Obesity:

Brawer R. et al.: Obesity and Cancer, Prim Care 2009, 36:509-513.

Dyslipidemia:

Ulmer H. et al.: Serum trigliceride concentrations and cancer risk in a large

cohort study in Austria, Br J Cancer 2009, August 18, Epub ahead of print.

High Blood Pressure: ??

Impaired Glucose Metabolism:

Ogunleye AA et al.: A cohort study of the risk of cancer associated with type

2 diabetes, Br J Cancer 2009, August 19, Epub ahead of print.

(Pancreas, Liver and Colon).

Type 2 diabetes mellitus:

Predictor of cancer mortality:

Evaluated in 467,922 men and 588,321 women in the USA with a follow-up

of 16 years.

Predictor in women: Colon carcinoma, pancreas

carcinoma, breast cancer.

Predictor in men: Liver and bladder carcinoma.

Coughlin SS, Calle EE, Teras LR et al. (2004):

Diabetes mellitus as a predictor of cancer mortality in a large cohort of US

adults.

Am J Epidemiol 15: 1160-1167.

Provocating epidemiological data:

Chronic insulin therapy (mitogenic

hormone/insulin-like growth receptors)

increases the risk of colorectal carcinoma.

Yang YX, Hennessy S, Lewis JD et al. (2004):

Insulin therapy and colorectal cancer risk among type 2 diabetes mellitus

patients.

Gastroenterology 12: 1044-1050.

Coherent strategic therapies of type 2

diabetes mellitus and cancer.

Non-pharmacologial management - diet

- physical activity

Principles of drug targets for T2DM and insulin

resistance and minimizing risk of contracting

cancer. Rapid progression of cancer disease. - Reducing excessive hepatic glucose production

- Treating ß-cells

- Targeting insulin signaling pathways

- Targeting lipid metabolism

The hidden story of cancer and

diabetes.

What is the cellular and molecular

science behind this discovery?

Critical role of impaired insulin release for development of T2DM

From: S.E. Kahn et al. Nature 444:840-846, 2006

Bitter Melon

Improves glucose and insulin sensitivity

in skeletal muscle.

Sridhar MG et al, BrJ Nutr (2008), 99:806-812.

Bitter Melon

Reduces lipogenesis in adipose tissue

and inhibits adipocyte hypertrophy.

Huang HL et al, BRJ Nutr(2008), 99:230-239.

lung: no functions for GLP-1 so far

GLP-1 receptor GLP-2 receptor

GLP-2:

Nutrient absorption

Hexose transport

Crypt cell proliferation

Activation of gut motility

Prevention of apoptosis

brain: GLP-1 triggers satiety and anxiety

stomach: GLP-1 delayes gastric emptying

intestinal L cells:

GLP-1 & GLP-2 production

pancreas (islets)

insulin secretion

beta cell proliferation

induction of islet neogenesis

prevention of beta cell apoptosis

Overview: The Glucagon Like Peptides: GLP-1 and GLP-2

Evid Based Complement Alternat. Med. 2013; 2013: 625892

Animal models

and

clinical studies

M. charantia

(n=30)

p-Wert*

M. charantia/

Chrom/ Zink

(n=35)

p-Wert*

Placebo

(n=32)

HbA1c-Wert

zu t0 [%]

6,47 ± 0,63

0,3431

0,400²

0,971³

6,69 ± 0,69

0,3431

0,400²

0,5294

6,51 ±

0,65

HbA1c-Wert

zu t4 [%]

6,28 ± 0,57

0,0861

0,096²

0,752³

6,65 ± 0,73

0,0861

0,096²

0,3554

6,42 ±

0,76

p-Wert*

0,002

0,401

0,041

* Die Berechnung der p-Werte erfolgte auf Basis der dekadisch logarithmierten HbA1c-

Werte

(Normalverteilung) 1 Gesamtvergleich der 3 Gruppen

² Vergleich Gruppe M. charantia vs. M. charantia/ Chrom/ Zink

³ Vergleich Gruppe M. charantia vs. Placebo 4 Vergleich Gruppe M. charantia/ Chrom/ Zink vs. Placebo

HbA1c-values before and after

intervention

HbA1c-values before and after

intervention

M. charantia/ Chrom/ Zink

M. charantia Placebo

7,0

6,8

6,6

6,4

6,2

6,0

Mitte

lwe

rt +

- 2

SE

HämoglobinA1c- Wert (%) zu t4

HämoglobinA1c- Wert (%) zu t0

p=0,041 p=0,002

Bitter Melon (Momordica charantia)

Peroxisome proliferator-activated receptors (PPARalpha,

PPARgamma, and PPARdelta) are physiological sensors for

glucose and lipid homeostasis. They are also the targets of

synthetic drugs; such as fibrates as PPARalpha agonists

which lower lipid level, and glitazones as PPARgamma

agonists which lower glucose level.

As diabetes and metabolic diseases are often associated with

high blood glucose and lipid levels, drugs that activate both

PPARalpha/gamma would be a logical approach. But

synthetically developed PPARalpha/gamma dual agonists

and glitazones are showing side effects such as weight gain

and edema. Therefore, natural compounds and their close

derivatives are focused as future drugs against metabolic

diseases.

Dual PPAR activator

(like „glitazars“)

Chuang CY,Hsu C, Chao CY et al:

Fractionation and identification of 9c, 11t, 13t-conjugated linolenic acid as

an activator of PPARalpha in bitter gourd (Momordica charantia).

J Biomed Sci(2006), 13:763-772.

Yasui Y, Hosokawa M, Sahara T et al:

Bitter gourd seed fatty acid rich 9c, 11t, 13t-conjugated linolenic acid

induces apoptosis and up-regulates the GADD45, p53 and PPARgamma

in human colon cancer Caco-2 cells.

Prostaglandins Leukot Essent Fatty Acids (2005), 73:113-119.

Bitter Melon

Increases glucose uptake and fatty acid

oxidation by:

i) GLUT4 translocation to the cell

membrane and

ii) activation of PPARalpha

Tan MJ et al, Chem.Biol.(2008),15:263-273.

Bitter Melon (Momordica charantia)