Sugar (glucose) is a carbohydrate, which is metabolized during aerobic respiration.
Glucose and oxygen are metabolized to release energy, with carbon dioxide and water as biproducts.
What happens to complex carbohydrates?
More complex carbohydrates are broken down (digested) into simple monomers including glucose, fructose, and galactose (80% glucose).
Glucose broken down in cells (when needed), or stored as glycogen.
Insulin is a peptide hormone produced by the beta cells of the islets of Langerhans in your pancreas in response to carbohydrate intake.
It is the main anabolic hormone of the body and promotes absorption of (primarily) glucose from the blood into liver, fat and muscle cells.
What is glucose converted into?
In these tissues, the glucose is either converted to glycogen or fats (triglycerides).
Reduced insulin signaling, or absence of insulin, leads to an increase in blood sugar, thus leading to diabetes mellitus (can be type 1 or type 2).
Diabetes is sometimes caused by destruction of the beta cells by an autoimmune reaction.
What other causes of increased sugar levels?
Other causes include accumulation of amyloid in the islet cells (much like Alzheimer’s!), leading to a disruption in function.
What genes (environemntal factors) have been associated with diabetes?
Genes associated with diabetes include genes required for beta-cell function, insulin processing or reception (insulin receptors), even mutations in insulin itself.
Disease also associated with environmental factors (e.g., viral infection or diet).
What is used to monitor how well a person controls their blood sugar?
To monitor how well a person controls their blood sugar, an A1C test for glycosylated hemoglobin is performed using blood.
This measures how much sugar is attached to the Hemoglobin (3 month snapshot, since RBCs live that long).
What are the typical values of A1C tests?
A normal A1C is below 5.7%, 6.5% or higher indicates diabetes, whereas 5.7% – 6.4% indicates a prediabetic condition.
What must be done to prevent complication from diabetes?
To stave off potential complications of diabetes (cardiovascular disease, neuropathies, retinopathies, chronic kidney disease leading to renal failure, amputations, etc.), levels around or below 7 should be achieved.
Elevated glucose levels (>80 mg/dL; hyperglycemia) contribute to these complications.
What consequences do low blood glucose levels have?
Low blood glucose levels (<80 mg/dL; hypoglycemia) also have consequences, including shakiness, anxiety, sweating, fatigue, irregular heart beat, hunger (craving for sugar!).
Can cause neuronal cell death in the brain (brain exclusively uses glucose for its energy!).
How can we continously monitor our blood levels?
A continuous glucose monitoring system can be used to monitor one’s glucose 24/7. Dexcom is the platform that I use, and it reads my sugar levels every 5 minutes.
Congenital anomalies of the kidney and urinary tract (CAKUT) are one of the more common sets of birth defects noted in children and represent a significant cause of morbidity and mortality, including end stage renal disease (ESRD).
Renal agenesis (RA) is defined as the complete absence of renal tissue at birth, can be separated into unilateral (URA) and bilateral (BRA) renal agenesis, and represents the most severe form of CAKUT.
URA vs. BRA
While URA can lead to proteinuria, hypertension and early renal failure, it is generally compatible with life. BRA, in contrast, is essentially fatal at birth.
What is the frequency of prevelance for BRA and URA?
It is estimated that BRA occurs at a frequency of 1/3000-1/5000 births, while URA occurs more frequently (up to 1/1000 births) although estimating the incidence is hampered by under-reporting.
How clinical conditions exist with RA as a component?
At least 70 different clinical conditions exist where RA has been identified as a component; the genetic basis of most cases has not been identified.
What are the three pathway groups that are generally associated with renal agenesis?
- Nuclear Proteins/Transcription Factors
- Secreted Factors
How has the mutation in rat models translated into humans?
Many of the genes identified in monogenic mutant animal models have not been adequately correlated with equivalent human disease.
However, soem genes have been associated with clefting (SPRY2): moreover, misregulation of retinoic acid signaling has been associated with orofacial clefts in mammals.
Describes the steps in kidney development...
What relation does GREB1 and GREB1L have to pronephros development?
GREB1 and GREB1L were both found to be in a chromatin complex with Estrogen Receptor as well as Retinoic Acid Receptor members – important in pronephros development.
How does the retinoic acid signaling play a role in pronephros development?
Several genes required for vertebrate pronephros specification and development (Pax2, Pax8, Lhx1, Wt1) are under the control of retinoic acid signaling, and mouse or human studies have associated these genes with renal agenesis.
How were the genes Pax2, Pax8, Lhx1, Wt1 confirmed as involved in the pronephros development?
Notably, zebrafish pax2a, pax8, lhx1a, and wt1a are all expressed in the intermediate mesoderm of the fish destined to become the pronephros, demonstrating a conservation of patterning factors.
What did a mutation in greb1l in zebrafish do?
A zebrafish mutant of greb1l presents with pronephric kidney defects! Animals die early with phenotypes consistent with an improperly functioning kidney.
What was the mutation in the Iowa family, Danish Family, a zebrafish with agenesis?
- A missense mutation in Iowa Family
- A framishift mutation in the Danish Family
- A nonsense mutation in the Zebrafish
All were mutations that occured in high conserved regions of the GREB1L gene.