The SA Journal Diabetes & Vascular Disease Vol 13 No 1 (July 2016)

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36 VOLUME 13 NUMBER 1 • JULY 2016
RESEARCH ARTICLE SA JOURNAL OF DIABETES & VASCULAR DISEASE
controlling NCDs in Uganda. A national NCD risk-factor survey
should however be undertaken to avoid biased generalisation of
results, as Kasese is not a representative population of Uganda.
Acknowledgements
We thank DANIDA through the Danish NCD Alliance – Uganda NCD
Alliance partnership for financial support for the data collection.
We also thank Dr Bahendeka Silver for his contribution during the
initial design of the study protocol. Ms Susanne Vilquarzt of the
Danish NCD Alliance was helpful in writing the grant application
to DANIDA. Ms Wandera Rebecca was helpful in data capture
and analysis. We thank the entire field staff in Kasese for the data
collection. We are grateful to Dr Hassan Sebina, the management
and staff at Kagando Hospital and Alcomed Clinics for their
invaluable input.
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Previous reports suggest that the
kallikrein-kinin system (KKS) could
be involved in insulin sensitisation and
glucose homeostasis. The KKS consists
of serine protease tissue kallikrein-1
(KLK-1), kinogens, bradykinin (BK) and lys-
bradykinin. BK has been shown to increase
insulin sensitivity and glucose uptake in rat
models; however, the role of KLK-1 is not
well known.
KLK-1 is a ‘ubiquitous 238 amino
acid glycoprotein [that] exists as a
heterogeneous mixture of glycoforms
due to variable glycosylation at three
potential sites’, according to a study
published recently in PLoS One. In pre-
clinical studies, KLK-1 has been shown to
significantly decrease blood pressure, and
insulin, glucose, plasma triglyceride and
cholesterol levels. However, these benefits
of KLK-1 were not characterised in terms
of dose, glycoform profile or activity.
To further investigate the characteristics
and benefits of KLK-1 for type 2 diabetes,
A novel treatment for type 2 diabetes patients
Kolodka and colleagues designed a
pre-clinical study involving DM199, a
recombinant human tissue kallikrein-1
protein (rhKLK-1). In this study, DM199
was produced from Chinese hamster ovary
cells. Its specific activity was measured in
vitro by cleavage of the substrate D-Val-Leu-
Arg-7 amido-4-trifluoromethyl coumarin,
and compared to the activity of porcine
kininogenase standard acquired from the
National Institute for Biological Standards
and Control. After the purification process,
DM199 was injected into obese rats and
mice for fasting blood glucose and oral
glucose tolerance tests.
The results from hyperinsulinaemic–
euglycaemic clamp studies indicated that
DM199 helped increase glucose infusion
rates and glucose disposal in non-diabetic
rats. In obese db/db mice, a single dose of
360 µg/kg of DM199 could significantly
reduce fasting blood glucose (FBG) and
post-prandial glucose levels. In Zucker
diabetic fatty (ZDF) rats, sub-acute dosing
of DM199 for seven days also increased
fasting insulin levels significantly. After the
sub-acute dosing period, FBG levels in ZDF
rats remained lower than controls during
the wash-out period.
According to the authors, the low FBG
levels observed in the rats after medium
and high doses of DM199 may have
been due to a protective effect on beta-
cell function or the stimulation effect on
insulin secretion. Based on the results of
this study, DM199 could be a potential
novel therapy for type 2 diabetes patients
due to its anti-hyperglycaemic effect.
1. Kolodka T, Charles ML, Raghavan A, et al.
Preclinical characterization of recombinant
human tissue kallikrein-1 as a novel treatment
for type 2 diabetes mellitus. PLoS One2014; 9(8):
e103981.Endocrinol 2014 August 6.
2.
3Adoi%2F10.1371%2Fjournal.pone.0103981.
3.
php?option=com_content&view=article&id=167
91&catid=1&Itemid=17.