| Recent
Patents on Endocrine, Metabolic & Immune Drug Discovery
ISSN: 1872-2148
Recent Patents on Endocrine,
Metabolic & Immune Drug Discovery
Volume 1, Number 3, November
2007
Contents
Signaling Pathways Involved in Physiopathology
of Pancreatic Beta-Cells Pp. 180-192
Stéphane Dalle, Safia Costes, Julie Quoyer, Gyslaine
Bertrand and Christophe Broca
[Abstract]
GLP-1 as a Therapeutic Agent in Patients with
Diabetes Mellitus Pp. 193-201
Ioannis Legakis
[Abstract]
Anti-Thrombotic Properties of Tomato
Pp. 202-209
Asim K. Duttaroy
[Abstract]
Therapeutic Use of Antioxidants in Sepsis
Pp. 210-223
Andre L. Rosario and Luciano C.P. Azevedo
[Abstract]
The Sodium Pump: Bridging the Basic
and Clinical Cardiovascular Sciences Pp. 224-246
Donald M. Foster, Suresh K. Verma, Hind Lal, John Reneau,
Manuela Smith and David E. Dostal
[Abstract]
Patents in Targets and Drugs for Insulin Resistance: Correlation
with Inflammatory Mediators Pp. 247-254
Daniel S. de Carvalho, Fernando R.M. da Silva Seixas and
Elizabeth P. Sampaio
[Abstract]
Patent Selections Pp. 255-257
Abstracts
[Back to top]
Signaling Pathways Involved in Physiopathology of Pancreatic
Beta-Cells
Stéphane Dalle, Safia Costes, Julie Quoyer, Gyslaine
Bertrand and Christophe Broca
Type 2 diabetes (T2D) is a heterogeneous disorder that
is characterized by chronic hyperglycemia and its prevalence
reaches epidemic proportions worldwide. T2D is characterized
by a progressive loss of the first phase of insulin secretion
in early stages of the disease. The origin of insulin secretion
failure is still unknown. As hyperglycemia becomes chronic,
pancreatic β-cell
undergoes deterioration and destruction. β-Cell
destruction by glucolipotoxic-mediated apoptosis and by proinflammatory
cytokines actions is important etiological factor in the progression
of the disease. The focus of this review is on the signaling
pathways engaged by G-protein coupled receptors and tyrosine-kinase
receptors which control β-cell
function and survival through cell kinases (i.e., cAMP/PKA,
IRS/PI3-kinase, and ERK1/2), and as well as on pathways implicated
in β-cell
dysfunction and death, among them glucotoxicity and lipotoxicity.
A better knowledge of these pathways (and of their dysfunctions)
will have significant implications for the prevention and
management of T2D (patents and design of new drug targets
for therapeutic approach), as well as for our general understanding
of β-cell
failure in this disease. Finally, the current and future molecular
targets for designing innovative therapeutic agents with the
aim to restore β-cell
mass and insulin secretion are reviewed.
[Back to top]
GLP-1 as a Therapeutic Agent in Patients with
Diabetes Mellitus
Ioannis Legakis
The gastrointestinal tract has a crucial role in the
control of energy homeostasis through the action of multiple
peptides known as incretins that act on distant target sites
to promote the efficient uptake and storage of energy. In
particular, GLP-1, an incretin hormone secreted from the intestinal
mucosa in response to meal ingestion, is shown to augment
the magnitude of meal-stimulated insulin secretion from islet
β cells
in a glucose-dependent manner and thus proved to be a novel
candidate for treatment in patients with diabetes mellitus.
This article reviews the biological actions of GLP-1 regulating
glucose homeostasis, with an emphasis on mechanisms of action
and the emerging therapeutic roles of GLP-1 analogues, and
DPP-4 inhibitors for the treatment of diabetes mellitus.
[Back to top]
Anti-Thrombotic Properties of Tomato
Asim K. Duttaroy
There is compelling evidence for tomatoes to be considered
as cardiovascular protective foods, due to the presence in
tomatoes of many nutrients which have been associated with
theoretical or proven effects on the cardiovascular system.
However, despite an inverse association found for high intakes
of tomato-based products, dietary lycopene was not strongly
associated with the risk of cardiovascular disease (CVD).
This indicates that other unidentified compounds in tomatoes
may have cardioprotective effects. We identified potent anti-platelet
factors in tomato extracts, which inhibited platelet aggregation
and discussed recent patents in this field. There is increasing
evidence that acute clinical manifestations of coronary atherosclerotic
disease are caused by plaque disruption and subsequent platelet-thrombus
formation. Platelet activity can influence the progression
of disease as well as the stability of atherosclerotic plaques.
The observed cardiovascular benefits attributed to the tomato
could be linked to antiplatelet activity and thus suppression
of platelet function in vivo. This type of natural
anti-thrombotic agent could have an application in primary
prevention of CVD.
[Back to top]
Therapeutic Use of Antioxidants in Sepsis
Andre L. Rosario and Luciano C.P. Azevedo
Sepsis is one of the most studied diseases in intensive
care medicine nowadays, mainly due to the severe morbidity
associated with this condition. Among the several mediators
evaluated in the context of sepsis, the study of reactive
oxygen and nitrogen species has achieved considerable interest,
mostly regarding their effects in direct cytotoxicity as well
as altered cell signaling. These compounds have also been
associated with vascular and organ dysfunction of sepsis.
The discovery of precise mechanisms of free radical-induced
organ dysfunction may lead to the discovery of therapeutic
strategies able to reduce the severe effects of sepsis in
the organism. In this context, the administration of antioxidants
has been tested in experimental and clinical studies of sepsis
in order to restore their adequate levels that are frequently
diminished during the course of disease. This review will
focus on mechanisms associated with increased oxidative stress
in sepsis, as well as therapeutic strategies concerning antioxidant
therapy during sepsis and multisystem organ failure. The most
recent patents related to the clinical use of antioxidants
in this field will also be discussed.
[Back to top]
The Sodium Pump: Bridging the Basic
and Clinical Cardiovascular Sciences
Donald M. Foster, Suresh K. Verma, Hind Lal, John Reneau,
Manuela Smith and David E. Dostal
Year 2007 is the golden anniversary for the discovery
of the sodium- and potassium adenosine triphosphatase, i.e.,
Na+, K+-ATPase,
or Na+-pump by Jens Skou
who shared the 1997 Nobel Prize in Chemistry for his discovery.
Prior to identification of the enzymatic basis of Na+
and K+ active transport by
Skou, the physiological and pharmacological manifestations
of such a system had long been evident. Since 1957, there
has been a dramatic increase in the knowledge of the physical,
chemical, and kinetic properties of the pump and recognition
of its basis for a wide range of physiological, pathological,
and pharmacological aspects of the cardiovascular system.
The Na+-pump has recently
been identified as a key partner in a wide array of cell signaling
pathways related to hypertrophy and expression of its marker
genes. Taken together, these facts make it evident that the
pump is a prime target for pharmacological interventions of
cardiovascular diseases such as hypertrophy, hypertension,
congestive heart failure (CHF), and preeclampsia. This review
couples basic attributes of the Na+-pump
with pathophysiological etiologies and clinical management
of cardiovascular related maladies, and also discusses related
patents.
[Back to top]
Patents in Targets and Drugs for Insulin Resistance: Correlation
with Inflammatory Mediators
Daniel S. de Carvalho, Fernando R.M. da Silva Seixas and
Elizabeth P. Sampaio
In the past decade the involvement of inflammatory responses
with metabolic disorders became well established, more specifically
the insulin resistance, responsible for Type-2 diabetes. The
major evidence for insulin resistance is the deactivation
of insulin receptors substrates (IRS) trough inflammatory
activated pathways and the presence of pro-inflammatory cytokines,
especially tumor necrosis factor alpha (TNFα
) at adipose tissues. The intracellular regulation
of TNFα
is mediated by several processes, thus the knowledge about
these pathways may provide targets to inhibit TNFα
synthesis, such as mitogen activated protein kinases
(MAPK) cascades and nuclear factor kappa B (NF-κB)
activation pathways. Natural anti-inflammatory pathways can
also be activated in order to treat or ameliorate these disorders,
such as peroxisome proliferator-activated receptors (PPAR)
and suppressors of cytokine signaling (SOCS) families. It
is discussed here international bibliography regarding insulin
resistance related to inflammation and also patent literature
disclosing methods to treat Type-2 diabetes targeting immune
systems molecules and pathways.
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