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Current Diabetes Reviews
ISSN: 1573-3998
Current Diabetes Reviews
Volume 3, Number 3, August 2007
Contents
Erectile Dysfunction and Diabetes Mellitus: Mechanistic
Considerations from Studies in Experimental Models
Pp. 149-158
Norman E. Cameron and Mary A. Cotter
[Abstract]
Fitness or Fatness - the Debate Continues for
the Role of Leptin in Obesity-Associated Heart Dysfunction
Pp. 159-164
Feng Dong and Jun Ren
[Abstract]
Taurine-Diabetes Interaction: From Involvement to
Protection Pp. 165-175
Sung-Jin Kim, Ramesh C. Gupta and Hyeon Woo Lee
[Abstract]
Physical Activity, Insulin Action, and Diabetes Prevention
and Control Pp. 176-184
Sheri R. Colberg
[Abstract]
Sympathetic Mechanisms of Hypoglycemic Counterregulation
Pp. 185-193
Robert P. Hoffman
[Abstract]
The Clinical Significance of IGF-I in Maternal Serum
During Pregnancy in Type 1 Diabetes Pp. 194-197
Finn Friis Lauszus
[Abstract]
Omega-3 Fatty Acids for Nutrition and Medicine: Considering
Microalgae Oil as a Vegetarian Source of EPA and DHA
Pp. 198-203
Scott D. Doughman, Srirama Krupanidhi and Carani B. Sanjeevi
[Abstract]
An Overview of the Effect of Weight Loss on Cardiovascular
Autonomic Function Pp. 204-211
Raelene E. Maser and M. James Lenhard
[Abstract]
Neuronal Histamine and its Receptors in Obesity and
Diabetes Pp. 212-216
Takayuki Masaki and Hironobu Yoshimatsu
[Abstract]
Abstracts
[Back to top]
Erectile Dysfunction and Diabetes Mellitus: Mechanistic
Considerations from Studies in Experimental Models
Norman E. Cameron and Mary A. Cotter
Diabetes is a major risk factor for erectile dysfunction.
The condition degrades both neural and vascular endothelium
penile control systems. Experimental and epidemiological evidence
suggest that both hyperglycemia and dyslipidemia contribute
to the etiology. These are the driving forces for elevated
oxidative stress and the formation of advanced glycation and
lipoxygenation end products, the major target being the nitric
oxide systems of nerve and endothelium. This causes reversible
functional loss followed by less reversible degenerative changes.
These mechanisms have direct effects, such as the nitric oxide
quenching, but perhaps more importantly, indirect effects
on the regulation of nitric oxide synthase expression and
activity, which can involve recruitment of proinflammatory
cell signaling pathways. The latter include protein kinase
C, mitogen-activated kinases, and the nuclear factor κ
B cascade. Diabetes also changes the trophic influences on
nerve and endothelium. Together, these form potential therapeutic
targets against diabetic erectile function, and indeed vascular
disease in general.
[Back to top]
Fitness or Fatness - the Debate Continues for
the Role of Leptin in Obesity-Associated Heart Dysfunction
Feng Dong and Jun Ren
Obesity is an independent risk factor for cardiovascular diseases.
As the first obese gene product identified, leptin participates
in many physiological processes. Besides its well known effects
on food intake and energy metabolism, leptin has been shown
to regulate cardiovascular function, glucose and lipid metabolism.
Although the precise role of leptin on cardiac health is still
at large, the peptide may initiate both hypertrophic and anti-hypertrophic
effects on hearts. Circulating leptin levels are believed
to correlate closely with body mass index (BMI) and total
amount of body fat, and predict change of heart morphology
and function. This is evidenced by that fact that compromised
cardiac function is present in both hyperleptinemic (db/db)
and hypoleptinemic (ob/ob) mouse models. Leptin replenishment
may reconcile depressed cardiac contractile function in ob/ob
mice, indicating the permissive effect of leptin on cardiac
function. Multiple signal pathways including NO, Jak/STAT,
p38 MAP kinase, ET-1 and NADPH oxidase have been implicated
to participate in the cardiac regulatory response of leptin.
In addition, elevated plasma leptin levels are speculated
to be an independent risk factor for cardiovascular diseases
such as hypertension and myocardial infarction. The current
dogma indicates that physiological range of leptin may be
essential for normal cardiomyocyte structure and function
whereas disrupted leptin signaling due to too much or too
little leptin may trigger functional and morphological alterations
leading to cardiac dysfunction.
[Back to top]
Taurine-Diabetes Interaction: From Involvement to
Protection
Sung-Jin Kim, Ramesh C. Gupta and Hyeon Woo Lee
Diabetes is a complex nature. To alleviate this, nutritional
intervention provides much scope and hope, and taurine has
been placed under this category successfully. An adult human
weighing 70 kg contains about 70 g taurine. Taurine in diabetes
has an age old story; taurine is involved in the development
and protection of insulin apparatus. Taurine and insulin both
have mutual stimulating actions with hypoglycemic properties.
On the clinical front, taurine supplementation has acceptable
beneficial effect in platelet aggregation and to name a few
more, in neuropathy, cardiomyopathy, nephropathy and retinopathy.
Recent studies have provided a role for taurine in fetal development
and also in blocking the transfer of diabetes from diabetic
mother to offspring. A number of mechanisms for taurine's
actions have been advocated, from osmoregulation to anti-oxidation.
Though sulfonylurea and recently introduced thiazolidinediones
are effective, they are also not free from complications,
thus needs to design new therapeutics. As taurine is also
a sulfonyl derivative and it will be of great interest to
develop taurine analogues as an alternative therapy. Considering
the great involvement of taurine in diabetes, this review
may provide a holistic view of taurine in diabetes and in
its prevention, in this century.
[Back to top]
Physical Activity, Insulin Action, and Diabetes Prevention
and Control
Sheri R. Colberg
Control of blood glucose levels in individuals with diabetes
mellitus (DM) is directly affected by the balance between
insulin and glucose-raising endocrine hormones, along with
other metabolic factors, including fuel use and availability,
exercise intensity and duration, training status, and visceral
fat levels, all of which can impact the effect of physical
activity on insulin action in diabetic or pre-diabetic individuals.
Current research suggests that type 2 DM can be prevented
and controlled with increased physical activity, largely through
improvements in the muscles’ sensitivity to insulin
that are affected by changes in both glucose and fat metabolism.
In addition, abnormal insulin action in the body is associated
with a host of other health conditions, including cardiovascular
disease and hyperten-sion, which can be better controlled
when their associations are fully understood. This article
discusses the importance of varying types of physical activity
on insulin action to enhance metabolic control and how they
can be undertaken safely by all diabetic individuals.
[Back to top]
Sympathetic Mechanisms of Hypoglycemic Counterregulation
Robert P. Hoffman
In normal individuals hypoglycemic counterregulation is a
multifactorial, redundant process that involves reduction
of insulin secretion, increasing glucagon secretion, adrenergic
activation, and increased growth hormone and cortisol secretion.
Metabolically, these lead to increased glucose production,
initially through glycogenolysis and later through gluconeogenesis,
decreased muscle glucose oxidation and storage and increased
release and use of alternative fuels, primarily free fatty
acids. They also lead to hypoglycemic symptoms and hunger
which increase food intake. These systems are designed to
provide as much glucose as possible for brain glucose use.
In patients with type 1 diabetes there are multiple impairments
of these responses. Insulin does not decrease. Glucagon secretion
is decreased or absent. Recovery from hypoglycemia is therefore
dependent on the adrenergic response. Hypoglycemia increases
plasma levels of both epinephrine and norepinephrine. These
catechols are released primarily from the adrenal medulla.
However, it is well documented that hypoglycemic increases
muscle sympathetic nerve activity, and that both α
and β
adrenergic activity increase. Increased β-activity
increases free fatty acid release which increase glucose production
and decrease glucose utilization. The increased α-adrenergic
activity’s primary role is to counteract β-adrenergic
vasodilation. It may also reduce neurogenic and neuroglycopenic
symptoms. Lastly, there is evidence that both cardiac and
adrenergic sensitivity are altered in type 1 diabetes. It
is hoped that this information can be used in the future to
help develop ways to protect patients with type 1 diabetes
from hypoglycemia and its adverse effects.
[Back to top]
The Clinical Significance of IGF-I in Maternal Serum
During Pregnancy in Type 1 Diabetes
Finn Friis Lauszus
Insulin-like growth factors (IGFs) constitute a system of
peptides that promote mitosis, growth, and organ development
by both paracrine and endocrine pathways, their bioavailability
being modulated by at least six specific IGF-binding proteins
(IGFBP). In type 1diabetic pregnancies IGF-I and –II
in maternal serum are associated with birth weight and their
action modulated by IGFBP-3 and phosporylated isoforms of
IGFBP-1. Pregnancy-associated plasma protein-A (PAPP-A), a
proteolytic substance of IGFBPs, is probably a modulator in
early diabetic pregnancy while human placental growth hormone
(hPGH) regulates the effect of IGF-I in pregnancy of diabetic
and non-diabetic pregnancies. IGF-I in maternal serum increases
concomitantly with progression of diabetic retinopathy despite
good glycemic control in pregnancy. The role of the new insulin
analogues in improving this effect has yet to be established.
Retinopathy in pregnancy is associated with an elevated level
of fibroblast growth factor-2 (FGF-2) and highly-phosphorylated
IGFBP-1, the latter further increasing the level of free IGF-I
and FGF-2. Thus, the effect on development of retinopathy
may be directly mediated by IGF-I or indirectly by a modifying
effect of IGFBP-3 and phophorylated isoforms of IGFBP-1 with
FGF-2 as a mediator.
[Back to top]
Omega-3 Fatty Acids for Nutrition and Medicine: Considering
Microalgae Oil as a Vegetarian Source of EPA and DHA
Scott D. Doughman, Srirama Krupanidhi and Carani B. Sanjeevi
Long-chain EPA/DHA omega-3 fatty acid supplementation can
be co-preventative and co-therapeutic. Current research suggests
increasing accumulated long chain omega-3s for health benefits
and as natural medicine in several major diseases. But many
believe plant omega-3 sources are nutritionally and therapeutically
equivalent to the EPA/DHA omega-3 in fish oil. Although healthy,
precursor ALA bio-conversion to EPA is inefficient and production
of DHA is nearly absent, limiting the protective value of
ALA supplementation from flax-oil, for example. Along with
pollutants certain fish acquire high levels of EPA/DHA as
predatory species. However, the origin of EPA/DHA in aquatic
ecosystems is algae. Certain microalgae produce high levels
of EPA or DHA. Now, organically produced DHA-rich microalgae
oil is available. Clinical trials with DHA-rich oil indicate
comparable efficacies to fish oil for protection from cardiovascular
risk factors by lowering plasma triglycerides and oxidative
stress. This review discusses 1) omega-3 fatty acids in nutrition
and medicine; 2) omega-3s in physiology and gene regulation;
3) possible protective mechanisms of EPA/DHA in major diseases
such as coronary heart disease, atherosclerosis, cancer and
type 2 diabetes; 4) EPA and DHA requirements considering fish
oil safety; and 5) microalgae EPA and DHA-rich oils and recent
clinical results.
[Back to top]
An Overview of the Effect of Weight Loss on Cardiovascular
Autonomic Function
Raelene E. Maser and M. James Lenhard
The prevalence of obesity is rising to epidemic proportions
in many countries worldwide. Obesity seriously increases an
individual’s risk of developing many health problems
including diabetes. Diabetes, like obesity, is also in epidemic
proportions with 300 million adults predicted to have the
disease by 2025. Investigating strategies for the prevention
and treatment of obesity and diabetes is vitally important.
Autonomic dysfunction is evident in both obesity and diabetes.
In persons with diabetes, impaired cardiovascular autonomic
activity is characterized by a reduction in parasympathetic
tone with a relative increase in sympathetic activity and
is specifically associated with a number of clinically significant
manifestations including exercise intolerance, intraoperative
cardiovascular lability, orthostatic hypotension, silent myocardial
ischemia, and increased risk of mortality. In obesity, parasympathetic
function is decreased while regional heterogeneity of increased
sympathetic activity may occur. Autonomic dysfunction increases
cardiovascular workload, hemodynamic stress, serious dysrhythmias,
and significant cardiac pathology. Thus, cardiac autonomic
imbalance may also be an important link between obesity and
increased morbidity and mortality. Beyond the obese and diabetic
state, multiple variables associated with these conditions
such as insulin, glucose, leptin, adiponectin and free fatty
acids have an affect on the autonomic nervous system.
Autonomic disturbances, however, appear to be reversible with
weight reduction. Since autonomic imbalance is a marker of
adverse risk, improvement obtained from weight loss should
be beneficial for the health of individuals with obesity and
diabetes. This overview will examine the relationship of the
autonomic nervous system in obesity and diabetes and explore
the effect of weight loss on autonomic function.
[Back to top]
Neuronal Histamine and its Receptors in Obesity and
Diabetes
Takayuki Masaki and Hironobu Yoshimatsu
Obesity is considered one of the risk factors for metabolic
disorders such as diabetes mellitus. There is increasing evidence
that obesity and diabetes are under the control of numerous
cytokines and hormones, such as adiponectin and leptin. In
addition, a number of studies have revealed that the brain
functions play a role in the development of obesity and diabetes
mellitus. Histamine and its receptors are classical inflammatory
mediators in peripheral tissues and also function in the brain.
The results of physiological and pharmacological studies revealed
that brain histamine and its receptors are involved in the
regulation of obesity and diabetes mellitus. Leptin has been
shown to regulate obesity and diabetes partially via brain
histamine and its receptors. In this review, we focused on
the roles of brain histamine and its receptors in regulating
obesity and diabetes mellitus.
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