Biochemical changes in rhesus monkey during the first days after streptozotocin administration are indicative of selective beta cell destruction.
Hormonal and glycemic changes in 22 rhesus monkeys were characterized during the first days after treatment with streptozotocin (STZ) (45 to 55 mg/kg, administered intravenously [IV]). Almost half (10/22) of the monkeys developed insulin-dependent diabetes mellitus (STZ-IDDM) within five days following injection. Four of the remaining monkeys did not become insulin dependent for at least 6 months after STZ treatment, during which time they were considered non-insulin-dependent, and eight monkeys never required exogenous insulin. In the STZ-IDDM group, plasma immunoreactive c-peptide (IRC-P) levels fell by three hours after STZ from a mean +/- SEM of 252 +/- 82 to 101 +/- 45 pg/mL, as glucose and immunoreactive glucagon (IRG) levels increased from 65 +/- 3 and 120 +/- 37, respectively, to 336 +/- 43 mg/dL and 234 +/- 52 pg/mL, respectively. Between six and 30 hours after treatment, IRC-P increased to a peak of 1,561 +/- 360 pg/mL before falling permanently to less than 60 pg/mL by 66 hours. During this period, glucose and IRG responded in a reciprocal fashion by falling and then increasing to levels above 300 mg/dL and 300 pg/mL, respectively, by 66 hours. In the non-insulin-dependent diabetes mellitus (STZ-NIDDM) group, no clear reciprocal relationship between IRC-P and glucose and IRG was obtained. In nine additional monkeys subjected to total pancreatectomy (Px), IRC-P and IRG levels fell immediately and permanently by greater than 90% and 75%, respectively. Levels of immunoreactive somatostatin increased steadily over the initial 96 hours following STZ, but did so both STZ-IDDM and Px monkey groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Takimoto
G
G
Department of Surgery, University of Illinois College of Medicine, Chicago.
Jones
C
C
Lands
W
W
Bauman
A
A
Jeffrey
J
J
Jonasson
O
O
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005609:Free Radicals; D005934:Glucagon / Q000097:blood; D006442:Glycated Hemoglobin / Q000032:analysis; D007515:Islets of Langerhans / Q000187:drug effects*; D008253:Macaca mulatta; D013311:Streptozocin / Q000633:toxicity*
D001786:Blood Glucose; D002096:C-Peptide; D005609:Free Radicals; D005934:Glucagon; D006442:Glycated Hemoglobin; D013311:Streptozocin