|
The
biochemical properties of adipocytes have been clearly established
in the medical literature. Depot-specific variances in said
properties are involved in the development of diabetes,
obesity, insulin-resistance, and weight gain.
Currently, type 2 diabetes is the most common metabolic
disease in the world, afflicting more than 120 million people.
Global scientific organizations have stated that by the
year 2010, more than 220 million people are projected to
have the disease by the year 2010 (1).
Insulin-related disorders, such as diabetes, obesity, and
insulin resistance are causally related as each of those
disorders are triggered by over-expression of blood glucose,
insulin, LPL, and their subsequent shunting of foods into
adipose tissue fat cell.
Peer reviewed, published studies have shown “A direct and
causative relationship between the accumulation of intracellular
fatty acid-derived metabolites and insulin resistance mediated
via alterations in the insulin signaling pathway, independent
of circulating adipocyte-derived hormones.”
As reported in 2005 Hypertension; 45:828, American
Heart Association; Mechanisms of Insulin Resistance
in Humans and Possible Links with Inflammation, “Although
standard definitions of insulin resistance still define
it in terms of the effects of insulin on glucose metabolism,
the last decade has seen a shift from the traditional "glucocentric"
view of diabetes to an increasingly acknowledged "lipocentric"
viewpoint.
This shift to lipocentric relationships in insulin resistance
has grown in popularity. As of 2007, scientists and research
endocrinologists have embraced the strong connection between
fat metabolism and insulin resistance.
Insulin resistance plays a primary role in the development
of type 2 diabetes mellitus, and the mechanism by which
insulin resistance occurs is related to alterations in fat
metabolism (2).
Clinically
defined, insulin resistance is “A state of reduced responsiveness
to normal circulating levels of insulin, which plays a major
role in the development of type 2 diabetes.”
It has been clearly demonstrated that insulin resistance
is a major factor in the pathogenesis of diabetes, obesity
and weight gain. Insulin resistance is biochemically tied
to Leptin and Lipoprotein Lipase (LPL).
In humans, the primary mechanism for fat storage is Lipoprotein
Lipase (LPL), known to scientists as the “Gatekeeper for
fat-storage in the fat cell.”
Orally
ingested agents, such as sugars, carbohydrates, and starches,
either stimulate LPL or negate its potent fat-storage sequence.
Fat-derived circulating hormones include Leptin, LPL, adipsin,
Acrp30/adipoQ (adipocyte complement-related protein of 30
kDa), and Resistin, all primary factors in causing whole-body
insulin resistance related to obesity (3).
The accumulation of intracellular fatty acid-derived metabolites
is triggered by a mechanism which causes tissue-specific
increase in LPL resulting in tissue-specific insulin resistance.
Overexpression of Lipoprotein Lipase, in either liver or
skeletal muscle, accumulates lipid (in corresponding tissue)
and proceeds to manifest insulin resistance in a tissue-specific
manner.
Fat-storage mechanisms in humans involve lipid accumulation
due to enhanced fatty acid uptake into the muscle coupled
with diminished mitochondrial lipid oxidation. Excess fatty
acids are esterified and take one-of-two pathways; they
are either stored or metabolized.
The storage versus metabolized routes to various
molecules results in the interference with normal cellular
signaling, particularly insulin-mediated signal transduction,
thus altering cellular and, subsequently, whole-body glucose
metabolism.
If not managed by dietary intervention, impaired insulin
responsiveness can progress to type 2 diabetes mellitus.
For the majority of the human population, this biochemical
cascade is avoidable, given that causes of intramyocellular
lipid deposition are predominantly diet and lifestyle-mediated.
Chronic
overconsumption of foods and beverages that stimulate LPL
have been shown to increase the risk of insulin resistance,
leading to type 2 diabetes, insulin resistance, obesity,
and weight gain.
Since LPL activity can be controlled by adjusting the consumption
of LPL-activating foods and drinks, LPL’s profound adipose
tissue fat-storing proclivities can be controlled by reducing/eliminating
dietary exposure to LPL-stimulating agents.
All
sweeteners, carbohydrates, sugars, starches, and other ingredients
used in prepared foods and beverages, as well as any raw
material, possess intrinsic biochemical characteristics
that determine their role in adipose tissue physiology,
including its LPL, insulinogenic, blood glucose, glycemic,
adipocyte, and fat-storing properties.
Studies of glucose disposal in normal humans shows that
skeletal muscle accounts for the majority of insulin-stimulated
glucose uptake and that more than 80 percent of this glucose
is then stored as glycogen. (Shulman GI et al. Quantitation
of muscle glycogen synthesis in normal subjects and subjects
with non-insulin-dependent diabetes by 13C nuclear magnetic
resonance spectroscopy. N Engl J Med. 1990; 322: 223–228)
The rate of glycogen synthesis in skeletal muscle is 50%
lower in diabetic subjects than in normal volunteers. The
only other organ capable of storing a significant amount
of glycogen is the liver, and glycogen stores are reduced
in diabetics.
This glycogen synthesis malfunction in type 2 diabetics
is mediated by dietary ingestion of high glycemic foods
and drinks, the majority of which contain LPL stimulating
ingredients, such as sucrose, glucose, dextrose, maltodextrins,
glucose polymers, and other high glycemic raw materials.
All high glycemic foods, drinks, and raw materials over-elevate
blood glucose levels, and negatively affect insulin and
LPL.
In
non-diabetics, dietary fat-storage mechanisms are
intrinsically the same as in diabetics, yet the reaction
in diabetics is profoundly more intense and has more serious
implications in blood glucose and insulin imbalance.
Glycogen
synthesis malfunction and vital muscle glycogen replenishment
cannot be controlled by ingestion of high glycemic carbohydrates,
sugars, and starches, which exacerbate insulin resistance,
LPL stimulation, and fat-storage into fat cells. Persons
with type 2 diabetes are, inevitably, overweight or obese;
conditions caused by continual ingestion of high glycemic
foods and drinks, as they cause LPL activation.
Artificial
sweeteners that have -0- calories, and -0- carbohydrates
do not replenish muscle glycogen, thus sports drinks with
-0- calories and -0- carbohydrates are contraindicated in
sports performance, as they can lead to “Hitting-the-Wall”
syndrome, reduced performance, and/or hypoglycemia.
The
human body, and particularly the brain, cannot function
in a -0- carbohydrate environment. Yet essential carbohydrates,
starches, sweeteners, and sugars used in all foods, beverages,
and edibles typically elicit high glycemic, fat-storage
properties, creating a biochemical cascade of reactive hypoglycemic,
sweet-cravings, LPL stimulation, impaired sports performance,
reduced cognitive function, and adipose tissue fat-storage.
In
1983, glycemic researchers began developing raw materials
that do not possess the metabolic activities of high glycemic
sugars, carbohydrates, and starches. In 1997, the process
for harvesting the Low Glycemic, Non Cephalic properties
from natural fruits had evolved into a feasible and affordable
alternative to synthetic and chemical raw materials that
stimulate LPL, imbalance Leptin, are high glycemic, and
that cause deposition of adipose tissue fat in humans.
The
natural fruit extracts are called SWEET INFUSED FRUITS ™.
They are derived from this proprietary process, do not stimulate
LPL, and have been Certified as “Low Glycemic.”
Following
a 20 + year research project, including use of SWEET INFUSED
FRUITS ™ in over 250,000 people over a 15 year-period, the
Low Glycemic carbohydrates, sugars, and starches derived
from SWEET INFUSED FRUITS ™ have been expanded to fulfill
market demand for Low Glycemic raw materials.
SWEET
INFUSED FRUITS ™ have undergone numerous Human In Vivo Clinical
Trials and has proven to be an “Anti-Carbohydrate” (4) in
diabetics and non-diabetics.
To
ascertain the interaction between SWEET INFUSED FRUITS ™
and Lipoprotein Lipase and Leptin, SWEET INFUSED FRUITS
™ were analyzed to determine thier “anti-carbohydrate” properties
and to quantify the precise mechanism by which they stunt
adipose tissue fat-storage.
Ramis
JM et al, Journal of Nutritional Biochemistry; 2005,
demonstrated that “The Leptin content of fat depots as well
as plasma insulin concentrations appear in our population
as the main determinants of adipose tissue LPL activity,
adjusted by gender, depot and BMI” and that “Tissue leptin
and plasma insulin are associated with lipoprotein lipase
activity in severely obese patients.”
To
this end, depot-related and gender-related variances in
LPL were examined in non-diabetic obese men and women. Endocrine
and biometric factors were rated for their dependence on
fat depot and gender. Activity and expression of Lipoprotein
Lipase (LPL) were analyzed in adipose tissue fat samples
from visceral and subcutaneous fat deposits.
The
all-natural SWEET INFUSED FRUITS ™, and their raw material
components, are suitable for inclusion in weight management
products, as well as all applications in Low Glycemic foods
and beverages.
Unlike
chemical and synthetic sweeteners, all-natural SWEET INFUSED
FRUITS ™ are suitable for children and pregnant women. Additionally,
SWEET INFUSED FRUITS ™ do not exacerbate ADD or Dyslexia,
and do not stimulate human LPL fat-storing mechanisms.
| (1) |
Shaw, J. E. , Zimmet, P. Z. , McCarty, D. & Courten,
M. D. (2000) Diabetes Care 23, Suppl. 2, B5-B10 |
| (2) |
Proceedings of the National Academy of Sciences of
the United States of America 2001; Tissue-specific
overexpression of lipoprotein lipase causes tissue-specific
insulin resistance . |
| (3)
|
2001;
Nature (London) 409, 307-312 Steppan, C. M. , Bailey,
S. T. , Bhat, S. , Brown, E. J. , Banerjee, R. R. ,
Wright, C. M. , Patel, H. R. , Ahima, R. S. & Lazar,
M. A. |
| (4)
|
Glycemic
Research Institute
www.Glycemic.com
Human In Vivo Clinical Trials
www.GlycemicIndexTesting.com |
American
Journal of Clinical Nutrition, Vol. 85, No. 3, 662-677,
March 2007. American Society for Nutrition
Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel
RL, Ferrante AW Jr. Obesity is associated with macrophage
accumulation in adipose tissue. J Clin Invest. 2003;
112: 1796–1808.
Shi H, Tzameli I, Bjorbaek C, Flier JS. Suppressor
of cytokine signaling 3 is a physiologic regulator
of adipocyte insulin signaling. J Biol Chem. 2004;
279: 34733–34740.
Bjorbaek C, El-Haschimi K, Frantz JD, Flier JS. The
role of SOCS-3 in leptin signaling and leptin resistance.
J Biol Chem. 1999; 274: 30059–30065.
Fain JN et al. Comparison of the release of adipokines
by adipose tissue, adipose tissue matrix, and adipocytes
from visceral and subcutaneous abdominal adipose tissues
of obese humans. Endocrinology. 2004; 145: 2273–2282.
Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole
J, Nichols A, Ross JS, Tartaglia LA, Chen H. Chronic
inflammation in fat plays a crucial role in the development
of obesity-related insulin resistance. J Clin Invest.
2003; 112: 1821–1830.
Havel PJ. Update on adipocyte hormones: regulation
of energy balance and carbohydrate/lipid metabolism.
Diabetes. 2004; 53 (suppl 1): S143–S151.
Kershaw EE, Flier JS. Adipose tissue as an endocrine
organ. J Clin Endocrinol Metab. 2004; 89: 2548–2556.
Nawrocki AR, Scherer PE. The delicate balance between
fat and muscle: adipokines in metabolic disease and
musculoskeletal inflammation. Curr Opin Pharmacol.
2004; 4: 281–289.
Berg AH, Combs TP, Scherer PE. ACRP30/adiponectin:
an adipokine regulating glucose and lipid metabolism.
Trends Endocrinol Metab. 2002; 13: 84–89.
Yamauchi T et al. Cloning of adiponectin receptors
that mediate antidiabetic metabolic effects. Nature.
2003; 423: 762–769.
McGarry JD. Banting lecture 2001: dysregulation of
fatty acid metabolism in the etiology of type 2 diabetes.
Diabetes. 2002; 51: 7–18.
Unger
RH, Orci L. Lipotoxic diseases of nonadipose tissues
in obesity. Int J Obes Relat Metab Disord. 2000; 24
(suppl 4): S28–S32.
Boden G, Shulman GI. Free fatty acids in obesity and
type 2 diabetes: defining their role in the development
of insulin resistance and beta-cell dysfunction. Eur
J Clin Invest. 2002; 32 (suppl 3): 14–23.
Jacob S. et al. Association of increased intramyocellular
lipid content with insulin resistance in lean nondiabetic
offspring of type 2 diabetic subjects. Diabetes. 1999;
48: 1113–1119.
Petersen KF, Hendler R, Price T, Perseghin G, Rothman
DL, Held N, Amatruda JM, Shulman GI. 13C/31P NMR studies
on the mechanism of insulin resistance in obesity.
Diabetes. 1998; 47: 381–386.
|
|
