Updated: 1/18/2019

Insulin and Glucagon

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Snapshot
  • A 15-year-old high school student presents with sudden weight loss, increased urination and increased thirst.  He is an otherwise healthy individual who plays soccer on his schools team.  On physical exam you see a lean young man with dry mucous membranes.  Fingerstick glucose reveals a blood glucose of 469 mg/dL.
Insulin Overview  
  • Synthesis/Release  
    • synthesized as proinsulin in β cells of pancreas
      • proinsulin = insulin + C-peptide
      • C-peptide secreted with insulin 
      • detection in serum is a mechanism to determine origin of hyperinsulinemia
        • present with endogenous insulin, but absent with exogenous administration  
    • hyperglycemia, GH, and cortisol ↑ insulin while hypoglycemia and somatostatin ↓ insulin secretion
    • β agonists ↑ release of insulin while α agonists ↓ insulin secretion
  • Function 
    • ↓ glucagon release by α cells of pancreas
    • ↑ Na+ retention (kidneys)
    • ↑ glycogen synthesis and storage
    • ↑ triglyceride synthesis and storage
      • recall babies of diabetic mothers are macrosomic
    • ↑ protein synthesis (muscles)
      • recall babies of diabetic mothers are macrosomic
    • ↑ cellular uptake of K+
      • recall used with glucose to treat hyperkalemia
    • ↑ glucose transport into skeletal muscle and adipose      
      • see Glucose transport topic
  • Pathology
    • a patient with an insulinoma will secrete abnormally high levels of insulin as well as C-peptide and will not produce anti-insulin antibodies
    • these patients will have severe hypoglycemia
Glucagon Overview
  • Production
    • secreted by the pancreas (alpha cells)
    • major stimulus for secretion is hypoglycemia
    • major inhibition of secretion in hyperglycemia
      • also inhibited by insulin and somatostatin
  • Function 
    • increase blood glucose
      • glycogenolysis
      • gluconeogenesis 
      • inhibition of insulin release
    • increase blood levels of other energy forms
      • lipolysis
      • ketone body production
  • Pathology
    • a glucogonoma is a tumor that secretes excess glucagon leading to hyperglycemia as well as the characteristic rash of necrolytic migratory erythema 
 

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Questions (7)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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(M1.EC.75) Pancreatic islets were isolated from a healthy, non-diabetic donor to perform an experiment to look at insulin secretion inhibition. Compounds would be added to separate wells containing the islets bathed in a high glucose solution for one hour. After one hour, the supernatant would be collected, and the insulin content would be measured with an enzyme-linked immunosorbent assay (ELISA). Which of the following compounds would result in the least insulin secretion when added to the islets? Review Topic

QID: 106862
1

Dobutamine

9%

(14/152)

2

Isoproterenol

16%

(24/152)

3

Tolbutamide

8%

(12/152)

4

Clonidine

43%

(66/152)

5

Glyburide

22%

(34/152)

M1

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SUBMIT RESPONSE 4

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(M1.EC.50) A researcher is tracing the fate of C-peptide, a product of preproinsulin cleavage. Which of the following is a true statement regarding the fate of C-peptide? Review Topic

QID: 100351
1

C-peptide is immediately degraded by the proteasome

0%

(0/22)

2

C-peptide is packaged with insulin in secretory vesicles

86%

(19/22)

3

C-peptide exits the cells via a protein channel

5%

(1/22)

4

C-peptide is further cleaved into insulin

5%

(1/22)

5

C-peptide activates an intracellular signaling cascade

0%

(0/22)

M1

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SUBMIT RESPONSE 2
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